Search (d4dr OR drd4 OR dopamine receptor D4) AND (ethanol OR alcohol OR alcoholic OR alcoholism) Limits: Publication Date from 1994/01/01 to 2003/12/31 Entrez pubmed Results Items 1 - 59 of 59 1: Lee HJ et al. D2 and D4 dopamine receptor g...[PMID: 12898574] Related Articles, Books, LinkOut PMID- 12898574 OWN - NLM STAT- MEDLINE DA - 20030804 DCOM- 20030917 LR - 20041215 PUBM- Print IS - 1552-4841 VI - 121 IP - 1 DP - 2003 Aug 15 TI - D2 and D4 dopamine receptor gene polymorphisms and personality traits in a young Korean population. PG - 44-9 AB - The correlation between the D4 dopamine receptor gene (DRD4) and the D2 dopamine receptor gene (DRD2) polymorphisms was investigated with personality traits. For this study, homogeneous population consisting of 243 young alcohol- and drug-naive Koreans who were blood-unrelated with a mean age (+/-SD) of 13.87 (+/-0.30) years old was analyzed for the DRD4 and the DRD2 polymorphisms with their personality trait by Temperament and character inventory (TCI). The association between Novelty seeking (NS) score and DRD4 long alleles was only observed among the female subjects (t = 2.11, P = 0.037), but not in the male counter part. Female subjects who carried the DRD2 less frequent alleles (TaqI A1, TaqI B1, and Intron6 1) showed higher RD4 scores (dependence vs. independence) of Reward dependence (RD) than those without these alleles (P < 0.05). There was no interaction between DRD4 and DRD2 on the personality traits. These results, thus, confirmed the previous findings in which the long repeats of the DRD4-exon III polymorphism are related to NS personality trait, and also suggested that the DRD2 less frequent alleles were also associated with the reward-dependent trait. CI - Copyright 2003 Wiley-Liss, Inc. AD - Department of Psychiatry, Korea University College of Medicine, Seoul, Korea. kuhj@netsgo.com FAU - Lee, Heon-Jeong AU - Lee HJ FAU - Lee, Hong-Seock AU - Lee HS FAU - Kim, Yong-Ku AU - Kim YK FAU - Kim, Leen AU - Kim L FAU - Lee, Min Soo AU - Lee MS FAU - Jung, In-Kwa AU - Jung IK FAU - Suh, Kwang-Yoon AU - Suh KY FAU - Kim, Sangduk AU - Kim S LA - eng PT - Journal Article PL - United States TA - Am J Med Genet B Neuropsychiatr Genet JID - 101235742 RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) SB - IM MH - Adolescent MH - Female MH - Gene Frequency MH - Humans MH - Korea MH - Male MH - Personality/*genetics MH - *Polymorphism, Genetic MH - Receptors, Dopamine D2/*genetics MH - Research Support, Non-U.S. Gov't EDAT- 2003/08/05 05:00 MHDA- 2003/09/18 05:00 AID - 10.1002/ajmg.b.20054 [doi] PST - ppublish SO - Am J Med Genet B Neuropsychiatr Genet 2003 Aug 15;121(1):44-9. PR -------------------------------------------------------------------------------- 2: Hutchison KE et al. Olanzapine reduces craving fo...[PMID: 12888781] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 12888781 OWN - NLM STAT- MEDLINE DA - 20030925 DCOM- 20031205 LR - 20041204 PUBM- Print IS - 0893-133X VI - 28 IP - 10 DP - 2003 Oct TI - Olanzapine reduces craving for alcohol: a DRD4 VNTR polymorphism by pharmacotherapy interaction. PG - 1882-8 AB - Separate investigations have suggested that olanzapine, a D4 antagonist, decreases craving after a priming dose of alcohol and that the DRD4 variable number of tandem repeats (VNTR) polymorphism influences the expression of craving after a priming dose of alcohol. The present study tested the hypothesis that olanzapine may be differentially effective at reducing cue-elicited craving based on individual differences in DRD4 VNTR in a sample of heavy social drinkers. Participants were randomly assigned to receive olanzapine (5 mg) or a control medication (cyproheptadine, 4 mg) prior to consuming three alcoholic drinks. Participants completed subjective measures of craving and euphoria after each drink. Participants who were homozygous or heterozygous for the 7 (or longer) repeat allele of the DRD4 VNTR were classified as DRD4 L, while the other participants were classified as DRD4 S. The findings indicated that olanzapine reduces craving for alcohol at baseline for both DRD4 S and DRD4 L individuals, but only reduces craving after exposure to alcohol cues and after a priming dose of alcohol for DRD4 L individuals. AD - Department of Psychology, University of Colorado at Boulder, Boulder, CO 80309-0345, USA. KentH@psych.colorado.edu FAU - Hutchison, Kent E AU - Hutchison KE FAU - Wooden, Angela AU - Wooden A FAU - Swift, Robert M AU - Swift RM FAU - Smolen, Andrew AU - Smolen A FAU - McGeary, John AU - McGeary J FAU - Adler, Lawrence AU - Adler L FAU - Paris, Lyndee AU - Paris L LA - eng GR - M01-RR00051/RR/NCRR GR - R01AA11473/AA/NIAAA PT - Clinical Trial PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Neuropsychopharmacology JID - 8904907 RN - 0 (Benzodiazepines) RN - 0 (Central Nervous System Depressants) RN - 0 (Receptors, Dopamine D2) RN - 0 (Serotonin Antagonists) RN - 0 (Serotonin Uptake Inhibitors) RN - 129-03-3 (Cyproheptadine) RN - 132539-06-1 (olanzapine) RN - 137750-34-6 (receptors, dopamine D4) RN - 28797-61-7 (Pirenzepine) RN - 64-17-5 (Ethanol) SB - IM MH - Adult MH - Affect/drug effects MH - Alcohol Drinking/*drug therapy/genetics MH - Behavior, Addictive/drug therapy/genetics MH - Benzodiazepines MH - Case-Control Studies MH - Central Nervous System Depressants MH - Chi-Square Distribution MH - Comparative Study MH - Cues MH - Cyproheptadine/therapeutic use MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Drug Interactions MH - Ethanol/adverse effects/pharmacology MH - Female MH - Humans MH - Individuality MH - Male MH - Minisatellite Repeats/*genetics MH - Pirenzepine/*analogs & derivatives/*therapeutic use MH - *Polymorphism, Genetic MH - Receptors, Dopamine D2/genetics MH - Research Support, U.S. Gov't, P.H.S. MH - Serotonin Antagonists/therapeutic use MH - Serotonin Uptake Inhibitors/*therapeutic use EDAT- 2003/07/31 05:00 MHDA- 2003/12/06 05:00 AID - 10.1038/sj.npp.1300264 [doi] AID - 1300264 [pii] PST - ppublish SO - Neuropsychopharmacology 2003 Oct;28(10):1882-8. DR -------------------------------------------------------------------------------- 3: Olson S. Population genetics. Seeking ...[PMID: 12434033] Related Articles, Substance via MeSH, Books, LinkOut PMID- 12434033 OWN - NLM STAT- MEDLINE DA - 20021115 DCOM- 20021212 LR - 20041204 PUBM- Print IS - 1095-9203 VI - 298 IP - 5597 DP - 2002 Nov 15 TI - Population genetics. Seeking the signs of selection. PG - 1324-5 FAU - Olson, Steve AU - Olson S LA - eng PT - News PL - United States TA - Science JID - 0404511 RN - 0 (Receptors, CCR5) RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) RN - EC 1.1.1.1 (Alcohol Dehydrogenase) SB - IM MH - Alcohol Dehydrogenase/genetics MH - Alleles MH - Genetic Predisposition to Disease MH - *Genetics, Medical MH - *Genetics, Population MH - Genome, Human MH - Heterozygote MH - Humans MH - Immunity, Natural MH - Linkage Disequilibrium MH - Mutation MH - Receptors, CCR5/genetics MH - Receptors, Dopamine D2/genetics MH - *Selection (Genetics) MH - Sequence Analysis, DNA MH - *Variation (Genetics) EDAT- 2002/11/16 04:00 MHDA- 2002/12/13 04:00 AID - 10.1126/science.298.5597.1324 [doi] AID - 298/5597/1324 [pii] PST - ppublish SO - Science 2002 Nov 15;298(5597):1324-5. NR -------------------------------------------------------------------------------- 4: Soyka M et al. Dopamine D 4 receptor gene po...[PMID: 12393313] Related Articles, Books, LinkOut PMID- 12393313 OWN - NLM STAT- MEDLINE DA - 20021023 DCOM- 20030321 LR - 20041204 PUBM- Print IS - 0022-3956 VI - 36 IP - 6 DP - 2002 Nov-Dec TI - Dopamine D 4 receptor gene polymorphism and extraversion revisited: results from the Munich gene bank project for alcoholism. PG - 429-35 AB - In 1998 a gene bank project for association studies in alcoholism was initiated at the Psychiatric Hospital of Munich. The research instruments used were partly adopted from the US collaborative study of the genetics of alcoholism and include the family history assessment module (FHAM), the semi-structured interview for assessment of genetics in alcoholism (SSAGA) and a number of personality inventories such as the Zuckerman's sensation-seeking scale, the NEO Five factor inventory and the temperament and character inventory. Based on the examination of 181 alcoholic subjects, no association was found between Dopamine D4 receptor gene polymorphism and novelty-seeking or extraversion as assessed by the three personality inventories. These findings are in line with a number of more recent studies questioning the association between novelty-seeking and DRD4 dopamine receptor gene polymorphism. Possible implications of these findings are discussed. CI - Copyright 2002 Elsevier Science Ltd. AD - Psychiatric Hospital of Ludwig-Maximilians-University Munich, Nussbaumstrasse 7, 80336 Munich, Germany. michael.soyka@psy.med.uni-muenchen.de FAU - Soyka, M AU - Soyka M FAU - Preuss, U W AU - Preuss UW FAU - Koller, G AU - Koller G FAU - Zill, P AU - Zill P FAU - Bondy, B AU - Bondy B LA - eng PT - Journal Article PL - England TA - J Psychiatr Res JID - 0376331 RN - 0 (DNA Primers) RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) SB - IM MH - Adult MH - Alcoholism/*genetics MH - Alleles MH - DNA Primers/genetics MH - Exploratory Behavior/physiology MH - *Extraversion (Psychology) MH - Female MH - Genotype MH - Humans MH - Male MH - Personality Inventory MH - Polymorphism, Genetic/*genetics MH - Receptors, Dopamine D2/*genetics EDAT- 2002/10/24 04:00 MHDA- 2003/03/22 04:00 AID - S0022395602000493 [pii] PST - ppublish SO - J Psychiatr Res 2002 Nov-Dec;36(6):429-35. DR -------------------------------------------------------------------------------- 5: Hutchison KE et al. The DRD4 VNTR polymorphism mo...[PMID: 11950104] Related Articles, Gene, HomoloGene, Compound via MeSH, Substance via MeSH, UniGene, GEO Profiles, Books, LinkOut PMID- 11950104 OWN - NLM STAT- MEDLINE DA - 20020412 DCOM- 20021016 LR - 20041204 PUBM- Print IS - 0278-6133 VI - 21 IP - 2 DP - 2002 Mar TI - The DRD4 VNTR polymorphism moderates craving after alcohol consumption. PG - 139-46 AB - Recent research has suggested that alterations in mesolimbic dopamine neurotransmission are central to the development and expression of craving for alcohol. Because the D4 dopamine receptor gene, variable numbers of tandem repeats (DRD4 VNTR) polymorphism putatively expresses functional differences in dopamine receptors, the present study tested whether this polymorphism influences the effects of a priming dose of alcohol on craving. Participants consumed 3 alcoholic drinks or 3 control drinks and completed measures of craving after each drink. Participants who were homozygous or heterozygous for the 7 (or longer) repeat allele were classified as DRD4 L, whereas the other participants were classified as DRD4 S. Results suggested that DRD4 L participants demonstrated significantly higher craving after consumption of alcohol as compared with the control beverage. AD - Department of Psychology, University of Colorado at Boulder, 80309-0345, USA. kenth@psych.colorado.edu FAU - Hutchison, Kent E AU - Hutchison KE FAU - McGeary, John AU - McGeary J FAU - Smolen, Andrew AU - Smolen A FAU - Bryan, Angela AU - Bryan A FAU - Swift, Robert M AU - Swift RM LA - eng GR - R01AA11473/AA/NIAAA PT - Clinical Trial PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Health Psychol JID - 8211523 RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) RN - 64-17-5 (Ethanol) SB - IM MH - Adult MH - Alcohol Drinking/*genetics MH - Alcoholism/*genetics MH - Analysis of Variance MH - Behavior, Addictive/genetics MH - Ethanol/*pharmacology MH - Female MH - Humans MH - Male MH - Minisatellite Repeats MH - *Polymorphism, Genetic MH - Receptors, Dopamine D2/*genetics MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, P.H.S. EDAT- 2002/04/13 10:00 MHDA- 2002/10/17 04:00 PST - ppublish SO - Health Psychol 2002 Mar;21(2):139-46. DR -------------------------------------------------------------------------------- 6: Falzone TL et al. Absence of dopamine D4 recept...[PMID: 11860516] Related Articles, Gene, GENSAT, Compound via MeSH, Substance via MeSH, UniGene, Nucleotide, Protein, GEO Profiles, Books, LinkOut PMID- 11860516 OWN - NLM STAT- MEDLINE DA - 20020225 DCOM- 20020425 LR - 20041204 PUBM- Print IS - 0953-816X VI - 15 IP - 1 DP - 2002 Jan TI - Absence of dopamine D4 receptors results in enhanced reactivity to unconditioned, but not conditioned, fear. PG - 158-64 AB - The prefrontal cortex receives a major dopaminergic input from the ventral tegmental area, which plays an important role in the integration of neuronal signals influencing behavioural responses to stressful environmental stimuli. The dopamine D4 receptor (D4R) is expressed at highest levels in the prefrontal cortex and is the predominant D2-like receptor localized in this brain area. To investigate the functional significance of D4Rs in dopamine-mediated responses we have analysed a strain of mice lacking this receptor subtype (Drd4-/-). Wild-type and Drd4-/- mice were challenged in two different approach/avoidance conflict paradigms: the elevated plus maze and the light/dark preference exploration test. By these behavioural measures Drd4-/- mice showed heightened avoidance to the more fear-provoking areas of each maze as demonstrated by reduced exploration of the open arms of the plus maze and longer latencies to explore the illuminated compartment of the light/dark shuttle box. These exaggerated avoidance behaviours were further enhanced by an additional handling stress but completely prevented by anxiolytic agents such as the benzodiazepine midazolam and ethanol. Although Drd4-/- mice displayed heightened anxiety, they exhibited normal ethanol preference and consumption in a two-bottle choice test. Learned fear responses evaluated by contextual, cued and instrumental fear-conditioning tests showed no difference between wild-type and Drd4-/- mice. Taken together these results indicate that the absence of D4Rs increases avoidance behaviour to unconditioned stimuli and does not impair behavioural reactions to Pavlovian fear-conditioning, suggesting that the D4R could play a key role in the dopaminergic modulation of cortical signals triggered by environmental stimuli. AD - Instituto de Investigaciones en Ingenieria Genetica y Biologia Molecular (CONICET) and Departamento de Ciencias Biologicas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina. FAU - Falzone, Tomas L AU - Falzone TL FAU - Gelman, Diego M AU - Gelman DM FAU - Young, Juan I AU - Young JI FAU - Grandy, David K AU - Grandy DK FAU - Low, Malcolm J AU - Low MJ FAU - Rubinstein, Marcelo AU - Rubinstein M LA - eng PT - Journal Article PL - France TA - Eur J Neurosci JID - 8918110 RN - 0 (Anti-Anxiety Agents) RN - 0 (Central Nervous System Depressants) RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) RN - 59467-70-8 (Midazolam) RN - 64-17-5 (Ethanol) SB - IM MH - Animals MH - Anti-Anxiety Agents/pharmacology MH - Anxiety/genetics/psychology MH - Avoidance Learning/physiology MH - Behavior, Animal/physiology MH - Central Nervous System Depressants/pharmacology MH - Conditioning (Psychology) MH - Conflict (Psychology) MH - Ethanol/pharmacology MH - Exploratory Behavior/physiology MH - Fear/*physiology MH - Mice MH - Mice, Knockout MH - Midazolam/pharmacology MH - Receptors, Dopamine D2/genetics/*physiology MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, Non-P.H.S. MH - Research Support, U.S. Gov't, P.H.S. MH - Stress, Psychological/genetics/psychology EDAT- 2002/02/28 10:00 MHDA- 2002/04/26 10:01 AID - 1842 [pii] PST - ppublish SO - Eur J Neurosci 2002 Jan;15(1):158-64. DR -------------------------------------------------------------------------------- 7: Pugsley TA et al. The discovery of PD 89211 and...[PMID: 11817497] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 11817497 OWN - NLM STAT- MEDLINE DA - 20020130 DCOM- 20020722 LR - 20041204 PUBM- Print IS - 0278-5846 VI - 26 IP - 2 DP - 2002 Feb TI - The discovery of PD 89211 and related compounds: selective dopamine D4 receptor antagonists. PG - 219-26 AB - The dopamine (DA) D2 family of receptors consists of the D2, D3, and D4 receptors. The DA D4 receptor is of interest as a target for drugs to treat schizophrenia based upon its high affinity for the atypical antipsychotic clozapine and its localization to the limbic and cortical regions of the brain. As part of a program to identify novel DA D4 receptor antagonists, a high-volume screen using the Parke-Davis compound library was initiated. This led to the discovery of PD 89211 (benzenemethanol, 2-chloro-4-[4-[(1H-benzimidazol-2-yl)methyl]-1-piperzinyl]) that displaced [3H]spiperone binding to hD4.2 with an affinity (Ki) of 3.7 nM. PD 89211 exhibited high selectivity for the DA D4.2 receptor (> 800-fold) as compared to other hDA receptor subtypes, rat brain serotonin, and adrenergic receptors. In vitro, PD 89211 had D4 receptor antagonist activity reversing quinpirole-induced [3H]thymidine uptake in CHOpro5 cells (IC50 = 2.1 nM). Limited structure-activity relationship (SAR) studies indicated that compounds with a 4-chloro-, 4-methyl-, and 3-chloro- substituents on the phenyl ring retained high affinity for D4 receptors, while those with a 4-methoxy- and no substituent had less affinity. While all clinically effective antipsychotics increase DA synthesis (DOPA accumulation) in rodents, PD 89211 did not increase DA synthesis in the DA-enriched striatum, indicating no effect on DA turnover and low propensity for exhibiting motor side effects. However, it did increase catecholamine synthesis in rat hippocampus, as did clozapine. Moreover, PD 89211 selectivity increased catecholamine synthesis in the hippocampus of wild type but not in mice lacking D4 receptors, suggesting that one function of D4 receptors may be to modulate DA/norepinephrine (NE) turnover in this brain area known to possess D4 receptors. The discovery of compounds like PD 89211 provides a tool to help in understanding the function of DA D4 receptors in the CNS. AD - CNS Pharmacology and Chemistry, Pfizer Global Research and Development, Ann Arbor, MI 48105, USA. thomas.pugsley@pfizer.com FAU - Pugsley, Thomas A AU - Pugsley TA FAU - Shih, Yu Hsin AU - Shih YH FAU - Whetzel, Steven Z AU - Whetzel SZ FAU - Zoski, Kim AU - Zoski K FAU - Van Leeuwen, Don AU - Van Leeuwen D FAU - Akunne, Hyacinth AU - Akunne H FAU - Mackenzie, R AU - Mackenzie R FAU - Heffner, Thomas G AU - Heffner TG FAU - Wustrow, David AU - Wustrow D FAU - Wise, Lawrence D AU - Wise LD LA - eng PT - Journal Article PL - England TA - Prog Neuropsychopharmacol Biol Psychiatry JID - 8211617 RN - 0 (Benzimidazoles) RN - 0 (Catecholamines) RN - 0 (Dopamine Antagonists) RN - 0 (PD 89211) RN - 0 (Piperazines) RN - 0 (Receptors, Dopamine D2) RN - 100-51-6 (Benzyl Alcohol) RN - 137750-34-6 (receptors, dopamine D4) SB - IM MH - Animals MH - Benzimidazoles/*chemistry/*pharmacology MH - Benzyl Alcohol/*pharmacology MH - CHO Cells MH - Catecholamines/metabolism MH - Dopamine Antagonists/*chemistry/*pharmacology MH - Dose-Response Relationship, Drug MH - Hamsters MH - Hippocampus/drug effects/metabolism MH - Humans MH - Male MH - Mice MH - Mice, Knockout MH - Piperazines/*chemistry/*pharmacology MH - Rats MH - Rats, Long-Evans MH - Receptors, Dopamine D2/*antagonists & inhibitors/metabolism EDAT- 2002/01/31 10:00 MHDA- 2002/07/23 10:01 PST - ppublish SO - Prog Neuropsychopharmacol Biol Psychiatry 2002 Feb;26(2):219-26. PR -------------------------------------------------------------------------------- 8: Milanes MV et al. Effects of morphine withdrawa...[PMID: 11697748] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 11697748 OWN - NLM STAT- MEDLINE DA - 20011107 DCOM- 20020403 LR - 20041117 PUBM- Print IS - 0008-4212 VI - 79 IP - 10 DP - 2001 Oct TI - Effects of morphine withdrawal on catecholaminergic neurons on heart right ventricle; implication of dopamine receptors. PG - 885-91 AB - The purpose of our study was to examine the effects of D1-and D2-dopamine receptors blockade on the changes in the ventricular content of catecholamines in rats withdrawn from morphine. Rats were given morphine by subcutaneous (s.c.) implantation of morphine pellets for 5 days. On the eighth day, morphine withdrawal was induced by s.c. administration of naloxone (1 mg/kg), and rats were killed 30 min later. Pretreatment with SCH 23390 (dopamine D1, D5 receptor antagonist) 15 min prior to naloxone administration suppressed some the behavioural signs of morphine withdrawal, whereas eticlopride (dopamine D2, D3, D4 receptor antagonist) did not. In addition, biochemical analysis indicate that SCH 23390 completely abolished the withdrawal-induced increase in noradrenaline and dopamine turnover in the right ventricle. By contrast, eticlopride did not block the hyperactivity of catecholaminergic neurons in the heart during morphine withdrawal. These data suggest that the hyperactivity of catecholaminergic neurons in the heart during morphine withdrawal is dependent upon D1 dopamine receptor activation. In addition, our results exclude the involvement of D2 dopamine receptors. AD - Department of Pharmacology, University School of Medicine, Murcia, Spain. FAU - Milanes, M V AU - Milanes MV FAU - Marin, M T AU - Marin MT FAU - Laorden, M L AU - Laorden ML LA - eng PT - Journal Article PL - Canada TA - Can J Physiol Pharmacol JID - 0372712 RN - 0 (Analgesics, Opioid) RN - 0 (Catecholamines) RN - 0 (Dopamine Antagonists) RN - 0 (Receptors, Dopamine) RN - 0 (Salicylamides) RN - 51-41-2 (Norepinephrine) RN - 51-61-6 (Dopamine) RN - 57-27-2 (Morphine) RN - 84226-12-0 (eticlopride) RN - 87075-17-0 ((R)-2,3,4,5-Tetrahydro-8-chloro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol) SB - IM MH - (R)-2,3,4,5-Tetrahydro-8-chloro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol/pha rmacology MH - *Analgesics, Opioid MH - Animals MH - Catecholamines/*physiology MH - Dopamine/metabolism MH - Dopamine Antagonists/pharmacology MH - Heart/drug effects/*innervation MH - Heart Ventricles/drug effects/metabolism/physiology MH - Male MH - *Morphine MH - Neurons/*physiology MH - Norepinephrine/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Dopamine/*drug effects MH - Research Support, Non-U.S. Gov't MH - Salicylamides/pharmacology MH - Substance Withdrawal Syndrome/*physiopathology EDAT- 2001/11/08 10:00 MHDA- 2002/04/04 10:01 PST - ppublish SO - Can J Physiol Pharmacol 2001 Oct;79(10):885-91. PR -------------------------------------------------------------------------------- 9: Ishige K et al. The activation of dopamine D4...[PMID: 11487630] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 11487630 OWN - NLM STAT- MEDLINE DA - 20010806 DCOM- 20010830 LR - 20041204 PUBM- Print IS - 1529-2401 VI - 21 IP - 16 DP - 2001 Aug 15 TI - The activation of dopamine D4 receptors inhibits oxidative stress-induced nerve cell death. PG - 6069-76 AB - Oxidative stress is thought to be the cause of nerve cell death in many CNS pathologies, including ischemia, trauma, and neurodegenerative disease. Glutamate kills nerve cells that lack ionotropic glutamate receptors via the inhibition of the cystine-glutamate antiporter x(c)(-), resulting in the inhibition of cystine uptake, the loss of glutathione, and the initiation of an oxidative stress cell death pathway. A number of catecholamines were found to block this pathway. Specifically, dopamine and related ligands inhibit glutamate-induced cell death in both clonal nerve cell lines and rat cortical neurons. The protective effects of dopamine, apomorphine, and apocodeine, but not epinephrine and norepinephrine, are antagonized by dopamine D4 antagonists. A dopamine D4 agonist also protects, and this protective effect is inhibited by U101958, a dopamine D4 antagonist. Although the protective effects of some of the catecholamines are correlated with their antioxidant activities, there is no correlation between the protective and antioxidant activities of several other ligands. Normally, glutamate causes an increase in reactive oxygen species (ROS) and intracellular Ca(2+). Apomorphine partially inhibits glutamate-induced ROS production and blocks the opening of cGMP-operated Ca(2+) channels that lead to Ca(2+) elevation in the late part of the cell death pathway. These data suggest that the protective effects of apomorphine on oxidative stress-induced cell death are, at least in part, mediated by dopamine D4 receptors via the regulation of cGMP-operated Ca(2+) channels. AD - Cellular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. FAU - Ishige, K AU - Ishige K FAU - Chen, Q AU - Chen Q FAU - Sagara, Y AU - Sagara Y FAU - Schubert, D AU - Schubert D LA - eng PT - Journal Article PL - United States TA - J Neurosci JID - 8102140 RN - 0 (Antioxidants) RN - 0 (Dopamine Agonists) RN - 0 (Dopamine Antagonists) RN - 0 (Neuroprotective Agents) RN - 0 (Reactive Oxygen Species) RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) RN - 51-41-2 (Norepinephrine) RN - 51-43-4 (Epinephrine) RN - 51-61-6 (Dopamine) RN - 56-86-0 (Glutamic Acid) RN - 58-00-4 (Apomorphine) RN - 641-36-1 (apocodeine) RN - 7440-70-2 (Calcium) RN - 7665-99-8 (Cyclic GMP) SB - IM MH - Animals MH - Antioxidants/metabolism/pharmacology MH - Apomorphine/*analogs & derivatives/pharmacology MH - Binding, Competitive/drug effects MH - Calcium/metabolism MH - Cell Death/drug effects/*physiology MH - Cell Line MH - Cyclic GMP/metabolism MH - Dopamine/metabolism/pharmacology MH - Dopamine Agonists/pharmacology MH - Dopamine Antagonists/pharmacology MH - Epinephrine/pharmacology MH - Glutamic Acid/metabolism MH - Hippocampus/cytology/drug effects/metabolism MH - Mice MH - Neurons/cytology/drug effects/metabolism MH - Neuroprotective Agents/pharmacology MH - Norepinephrine/pharmacology MH - Oxidative Stress/drug effects MH - Rats MH - Reactive Oxygen Species/metabolism MH - Receptors, Dopamine D2/agonists/antagonists & inhibitors/*metabolism MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, Non-P.H.S. MH - Research Support, U.S. Gov't, P.H.S. EDAT- 2001/08/07 10:00 MHDA- 2001/08/31 10:01 AID - 21/16/6069 [pii] PST - ppublish SO - J Neurosci 2001 Aug 15;21(16):6069-76. NR -------------------------------------------------------------------------------- 10: Rothhammer F et al. [Genetics of addictive disord...[PMID: 11347517] Related Articles, Books, LinkOut PMID- 11347517 OWN - NLM STAT- MEDLINE DA - 20010511 DCOM- 20010614 LR - 20041117 PUBM- Print IS - 0034-9887 VI - 128 IP - 11 DP - 2000 Nov TI - [Genetics of addictive disorders] PG - 1279-82 AB - Given the spectacular advances of genetics during the last five years, it seems appropriate to revisit the important subject of genetics of alcoholism and substance abuse. In recent studies alcohol abuse was shown to have an hereditability of roughly 38%, whereas psychostimulant and opiate use exhibit hereditabilities of 11 to 45%. The hereditability of smoking was found to be around 50%. There is a strong comorbidity between alcoholism and smoking. More than 80% of alcoholics smoke cigarettes in the U.S.A. Other genetic methods such as linkage analysis, allele sharing methods, association studies and analysis of inbred, transgenic and gene-knockout rodents, have partially agreed in showing that the 5HT-1B serotonin receptor and the DRD1, DRD2 and DRD4 dopamine receptors, as well as the dopamine transporter DAT, play an important role in behaviors related to alcoholism and substance abuse. Some neurochemical markers, as for example monoamine oxidase and adenylate cyclase have also been implicated in addictive disorders. The aldehyde dehydrogenase allele ALDH2*2 has a protective effect against alcoholism. Two whole genome linkage studies have shown linkage to chromosomal regions that are in the proximity of the DRD4 dopamine receptor, the GABA receptor gene cluster and the alcohol dehydrogenase gene cluster. AD - Programa de Genetica Humana, Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. FAU - Rothhammer, F AU - Rothhammer F FAU - Rothhammer, P AU - Rothhammer P FAU - Llop, E AU - Llop E LA - spa PT - Journal Article PT - Review PT - Review, Tutorial TT - Genetica de los desordenes adictivos. PL - Chile TA - Rev Med Chil JID - 0404312 RN - 0 (Biological Markers) SB - IM MH - Alcoholism/genetics MH - Behavior, Addictive/*genetics MH - Biological Markers MH - English Abstract MH - Humans MH - Smoking/genetics MH - Substance-Related Disorders/genetics RF - 21 EDAT- 2001/05/12 10:00 MHDA- 2001/06/15 10:01 PST - ppublish SO - Rev Med Chil 2000 Nov;128(11):1279-82. DR -------------------------------------------------------------------------------- 11: Feng J et al. An in-frame deletion in the a...[PMID: 11317218] Related Articles, Books, LinkOut PMID- 11317218 OWN - NLM STAT- MEDLINE DA - 20010424 DCOM- 20010628 LR - 20041117 PUBM- Print IS - 1359-4184 VI - 6 IP - 2 DP - 2001 Mar TI - An in-frame deletion in the alpha(2C) adrenergic receptor is common in African--Americans. PG - 168-72 AB - alpha(2) adrenergic receptors are activated by adrenaline and noradrenaline, and three subtypes (ie, A, B, C) have differential affinities for antagonists and medications. The alpha(2c) adrenergic receptor (ADRA2C), located on chromosome 4p16.3, is a candidate gene for schizophrenia because it binds clozapine, an atypical neuroleptic useful for treatment-resistant schizophrenia. In addition, ADRA2C binds clonidine which is prescribed for three psychiatric diseases. This report communicates the findings of the genetic scanning of this gene of very tough GC content. The complete coding sequences and splice junctions were scanned with [DOVAM]-S in 104 schizophrenics, and pilot probes of patients with alcoholism (41 patients), cocaine abuse (25 patients), puerperal psychosis (30 patients), attention deficient/hyperactivity disorder (25 patients) and autism (25 patients). Six sequence variants were found, including five silent polymorphisms (allele frequencies 0.6--25%) and an in-frame deletion of a homologous repeat at nucleotides 967--978 (ie, TIDRU(1)). Genotyping of the normal two repeat unit of the Third Intracytoplasmic Domain Repeat Unit (TIDRU(2)) and the deleted variant (TIDRU(1)) revealed that TIDRU(1) had allelic frequencies of 39% (11/28) and 3.5% (6/172) in African-American and Caucasian schizophrenics, respectively, and it occurred with equal frequency in controls (44%, 31/70 and 3.0%, 6/198). TIDRU(1) occurs at a location similar to the third intracytoplasmic 48-nucleotide repeat unit in the DRD4 that is associated with ADHD. Although these data do not suggest an association of TIDRU(1) with schizophrenia, additional studies are needed to see whether TIDRU(1) confers a clinical phenotype. AD - Department of Molecular Genetics, City of Hope National Medical Center & Beckman Research Institute, 1500 East Duarte Road, Duarte, CA 91010, USA. FAU - Feng, J AU - Feng J FAU - Zheng, J AU - Zheng J FAU - Gelernter, J AU - Gelernter J FAU - Kranzler, H AU - Kranzler H FAU - Cook, E AU - Cook E FAU - Goldman, D AU - Goldman D FAU - Jones, I R AU - Jones IR FAU - Craddock, N AU - Craddock N FAU - Heston, L L AU - Heston LL FAU - Delisi, L AU - Delisi L FAU - Peltonen, L AU - Peltonen L FAU - Bennett, W P AU - Bennett WP FAU - Sommer, S S AU - Sommer SS LA - eng PT - Journal Article PL - England TA - Mol Psychiatry JID - 9607835 RN - 0 (RNA Splice Sites) RN - 0 (Receptors, Adrenergic, alpha-2) SB - IM MH - African Continental Ancestry Group/*genetics MH - Case-Control Studies MH - Female MH - *Gene Deletion MH - Humans MH - Male MH - Polymorphism, Genetic MH - RNA Splice Sites/genetics MH - Receptors, Adrenergic, alpha-2/*genetics MH - Research Support, Non-U.S. Gov't MH - Schizophrenia/*ethnology/*genetics EDAT- 2001/04/24 10:00 MHDA- 2001/06/29 10:01 PHST- 1999/11/19 [received] PHST- 2000/08/03 [revised] PHST- 2000/08/03 [accepted] AID - 10.1038/sj/mp/4000817 [doi] PST - ppublish SO - Mol Psychiatry 2001 Mar;6(2):168-72. NR -------------------------------------------------------------------------------- 12: Bau CH et al. DRD4 and DAT1 as modifying ge...[PMID: 11244477] Related Articles, Books, LinkOut PMID- 11244477 OWN - NLM STAT- MEDLINE DA - 20010313 DCOM- 20010510 LR - 20050119 PUBM- Print IS - 1359-4184 VI - 6 IP - 1 DP - 2001 Jan TI - DRD4 and DAT1 as modifying genes in alcoholism: interaction with novelty seeking on level of alcohol consumption. PG - 7-9 FAU - Bau, C H AU - Bau CH FAU - Almeida, S AU - Almeida S FAU - Costa, F T AU - Costa FT FAU - Garcia, C E AU - Garcia CE FAU - Elias, E P AU - Elias EP FAU - Ponso, A C AU - Ponso AC FAU - Spode, A AU - Spode A FAU - Hutz, M H AU - Hutz MH LA - eng PT - Letter PL - England TA - Mol Psychiatry JID - 9607835 RN - 0 (Carrier Proteins) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Receptors, Dopamine D2) RN - 0 (dopamine transporter proteins) RN - 137750-34-6 (receptors, dopamine D4) SB - IM MH - Alcohol Drinking/*genetics MH - Alcoholism/*genetics MH - Carrier Proteins/*genetics MH - *Exploratory Behavior MH - Gene Frequency MH - Humans MH - *Membrane Glycoproteins MH - *Membrane Transport Proteins MH - *Nerve Tissue Proteins MH - Receptors, Dopamine D2/*genetics EDAT- 2001/03/13 10:00 MHDA- 2001/05/22 10:01 PST - ppublish SO - Mol Psychiatry 2001 Jan;6(1):7-9. DR -------------------------------------------------------------------------------- 13: Ozkaragoz T et al. Extraversion. Interaction bet...[PMID: 11163121] Related Articles, Books, LinkOut PMID- 11163121 OWN - NLM STAT- MEDLINE DA - 20010222 DCOM- 20010405 LR - 20041117 PUBM- Print IS - 0741-8329 VI - 22 IP - 3 DP - 2000 Nov TI - Extraversion. Interaction between D2 dopamine receptor polymorphisms and parental alcoholism. PG - 139-46 AB - Both molecular genetic factors (the D2 dopamine receptor (DRD2) and the D4 dopamine receptor (DRD4) polymorphisms) and environmental influences of living in an alcoholic or nonalcoholic home on the personality traits of Extraversion and Neuroticism were assessed in drug-naive, young adolescent boys. There were no significant main effects of genetic or environmental factors on either Neuroticism or Extraversion as measured by the Junior Eysenck Personality Inventory (JEPI). However, a significant interaction between DRD2 (but not DRD4) alleles and environmental variables was observed on Extraversion. Specifically, children with the minor alleles of the DRD2 gene showed a significantly greater Extraversion score when living in an alcoholic than in a nonalcoholic home. In contrast, children with the major alleles of the DRD2 gene showed a trend in the opposite direction. Although the results are preliminary and pending replication, they nevertheless provide the first report of a specific gene-environment interaction involving a human personality trait. AD - Department of Psychiatry and Biobehavioral, University of California Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024-1759, USA. FAU - Ozkaragoz, T AU - Ozkaragoz T FAU - Noble, E P AU - Noble EP LA - eng GR - AA11573/AA/NIAAA PT - Journal Article PL - United States TA - Alcohol JID - 8502311 RN - 0 (Receptors, Dopamine D2) SB - IM MH - Adolescent MH - Alcoholism/*genetics MH - Alleles MH - Child MH - Environment MH - *Extraversion (Psychology) MH - Humans MH - Male MH - Personality/genetics MH - *Polymorphism, Genetic MH - Receptors, Dopamine D2/*genetics MH - Research Support, U.S. Gov't, P.H.S. EDAT- 2001/02/13 11:00 MHDA- 2001/04/06 10:01 AID - S0741832900001129 [pii] PST - ppublish SO - Alcohol 2000 Nov;22(3):139-46. DR -------------------------------------------------------------------------------- 14: Comings DE et al. Reward deficiency syndrome: g...[PMID: 11105655] Related Articles, OMIM, Cited in PMC, Books, LinkOut PMID- 11105655 OWN - NLM STAT- MEDLINE DA - 20001208 DCOM- 20010118 LR - 20041204 PUBM- Print IS - 0079-6123 VI - 126 DP - 2000 TI - Reward deficiency syndrome: genetic aspects of behavioral disorders. PG - 325-41 AB - The dopaminergic and opioidergic reward pathways of the brain are critical for survival since they provide the pleasure drives for eating, love and reproduction; these are called 'natural rewards' and involve the release of dopamine in the nucleus accumbens and frontal lobes. However, the same release of dopamine and production of sensations of pleasure can be produced by 'unnatural rewards' such as alcohol, cocaine, methamphetamine, heroin, nicotine, marijuana, and other drugs, and by compulsive activities such as gambling, eating, and sex, and by risk taking behaviors. Since only a minority of individuals become addicted to these compounds or behaviors, it is reasonable to ask what factors distinguish those who do become addicted from those who do not. It has usually been assumed that these behaviors are entirely voluntary and that environmental factors play the major role; however, since all of these behaviors have a significant genetic component, the presence of one or more variant genes presumably act as risk factors for these behaviors. Since the primary neurotransmitter of the reward pathway is dopamine, genes for dopamine synthesis, degradation, receptors, and transporters are reasonable candidates. However, serotonin, norepinephrine, GABA, opioid, and cannabinoid neurons all modify dopamine metabolism and dopamine neurons. We have proposed that defects in various combinations of the genes for these neurotransmitters result in a Reward Deficiency Syndrome (RDS) and that such individuals are at risk for abuse of the unnatural rewards. Because of its importance, the gene for the [figure: see text] dopamine D2 receptor was a major candidate gene. Studies in the past decade have shown that in various subject groups the Taq I A1 allele of the DRD2 gene is associated with alcoholism, drug abuse, smoking, obesity, compulsive gambling, and several personality traits. A range of other dopamine, opioid, cannabinoid, norepinephrine, and related genes have since been added to the list. Like other behavioral disorders, these are polygenically inherited and each gene accounts for only a small per cent of the variance. Techniques such as the Multivariate Analysis of Associations, which simultaneously examine the contribution of multiple genes, hold promise for understanding the genetic make up of polygenic disorders. AD - Department of Medical Genetics, City of Hope Medical Center, Duarte, CA 91010, USA. dcomings@earthlink.net FAU - Comings, D E AU - Comings DE FAU - Blum, K AU - Blum K LA - eng PT - Journal Article PT - Review PL - NETHERLANDS TA - Prog Brain Res JID - 0376441 RN - 0 (Carrier Proteins) RN - 0 (Central Nervous System Stimulants) RN - 0 (Neurotransmitters) RN - 0 (Opioid Peptides) RN - 0 (Receptors, Adrenergic) RN - 0 (Receptors, Cannabinoid) RN - 0 (Receptors, Dopamine D2) RN - 0 (Receptors, Drug) RN - 0 (Receptors, Neurotransmitter) RN - 137750-34-6 (receptors, dopamine D4) RN - EC 1.14.17.1 (Dopamine beta-Hydroxylase) RN - EC 1.4.3.4 (Monoamine Oxidase) SB - IM MH - Attention Deficit Disorder with Hyperactivity/genetics MH - Behavior, Addictive/genetics MH - Carrier Proteins/genetics/physiology MH - Central Nervous System Stimulants/pharmacology MH - Compulsive Behavior/*genetics MH - Dangerous Behavior MH - Dopamine beta-Hydroxylase/genetics MH - Exploratory Behavior MH - Genetic Heterogeneity MH - Genetic Predisposition to Disease MH - Humans MH - Impulsive Behavior/*genetics MH - Models, Neurological MH - Monoamine Oxidase/genetics MH - Neurotransmitters/metabolism/*physiology MH - Nucleus Accumbens/drug effects/physiology MH - Opioid Peptides/genetics/physiology MH - Polymorphism, Restriction Fragment Length MH - Prefrontal Cortex/drug effects/physiology MH - Receptors, Adrenergic/drug effects/genetics MH - Receptors, Cannabinoid MH - Receptors, Dopamine D2/drug effects/genetics/physiology MH - Receptors, Drug/drug effects/genetics MH - Receptors, Neurotransmitter/drug effects/*genetics/physiology MH - *Reward MH - Satiation/physiology MH - Self Stimulation/physiology MH - Stress Disorders, Post-Traumatic/genetics/physiopathology MH - Substance-Related Disorders/genetics MH - Tourette Syndrome/genetics/physiopathology RF - 152 EDAT- 2000/12/06 11:00 MHDA- 2001/02/28 10:01 PST - ppublish SO - Prog Brain Res 2000;126:325-41. DR -------------------------------------------------------------------------------- 15: Malhotra AK et al. The dopamine D(4) receptor ge...[PMID: 11058499] Related Articles, Books, LinkOut PMID- 11058499 OWN - NLM STAT- MEDLINE DA - 20001114 DCOM- 20001130 LR - 20041204 PUBM- Print IS - 0002-953X VI - 157 IP - 11 DP - 2000 Nov TI - The dopamine D(4) receptor gene and novelty seeking. PG - 1885-6 FAU - Malhotra, A K AU - Malhotra AK FAU - Goldman, D AU - Goldman D LA - eng PT - Comment PT - Letter PL - UNITED STATES TA - Am J Psychiatry JID - 0370512 RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) SB - AIM SB - IM CON - Am J Psychiatry. 1999 Sep;156(9):1453-5. PMID: 10484963 MH - Alcoholism/diagnosis/genetics/psychology MH - Cohort Studies MH - Exploratory Behavior/*physiology MH - Finland MH - Gene Frequency/physiology MH - Humans MH - Personality Disorders/diagnosis/genetics/psychology MH - Polymorphism, Genetic/genetics MH - Receptors, Dopamine D2/*genetics/physiology MH - Substance-Related Disorders/diagnosis/*genetics/psychology EDAT- 2000/11/04 11:00 MHDA- 2001/02/28 10:01 PST - ppublish SO - Am J Psychiatry 2000 Nov;157(11):1885-6. PR -------------------------------------------------------------------------------- 16: Granger NA et al. Pharmacological characterizat...[PMID: 10876119] Related Articles, Compound via MeSH, Substance via MeSH, Cited in PMC, Books, LinkOut PMID- 10876119 OWN - NLM STAT- MEDLINE DA - 20001107 DCOM- 20001107 LR - 20041117 PUBM- Print IS - 0965-1748 VI - 30 IP - 8-9 DP - 2000 Aug-Sep TI - Pharmacological characterization of dopamine receptors in the corpus allatum of Manduca sexta larvae. PG - 755-66 AB - Dopamine receptors previously identified in corpora allata (CA) of Manduca sexta last instars on the basis of dopamine effects on JH (juvenile hormone)/JH acid biosynthesis and cyclic AMP (cAMP) accumulation, were characterized pharmacologically. For this study, a broad spectrum of agonists or antagonists of D1, D2, D3 or D4 dopamine receptors, together with the dopamine metabolite N-acetyl-dopamine, other neurotransmitters and their agonists/antagonists, were tested for their effects on gland activity and cAMP production. The lack of effect of other neurotransmitters supports the specificity of the effect of dopamine and the dopamine specificity of the receptors. Only the D2 receptor antagonist spiperone had a potent effect on JH biosynthesis and cAMP formation by CA taken on day 0 of the last stadium, when dopamine stimulates both activities and thus appears to be acting via a D1-like receptor. Several other D2 receptor antagonists, and D1, D2/D1 and D4,3/D2 receptor antagonists were less effective. Thus, the D1-like receptor of the Manduca CA appears to be distinct pharmacologically from vertebrate D1 receptors. By contrast, a number of D2 agonists/antagonists had a significant effect on JH acid biosynthesis and cAMP production by the CA from day 6 of the last stadium, when dopamine inhibits both activities and thus appears to be acting via a D2-like receptor. Certain D1-specific agonists/antagonists were equally effective. The Manduca D2-like receptor therefore bears some pharmacological resemblance to vertebrate D2 receptors. N-acetyl dopamine acted as a dopamine agonist with day 6 CA, the first identified function for an N-acetylated biogenic amine in insects. Dopamine was found to have the same differential affect on the formation of cAMP in homogenates of day 0 and day 6 brains as it did with CA, and in the same concentration range. Dopamine receptor agonists/antagonists affecting cAMP formation by day 0 and day 6 CA homogenates had similar effects with brain homogenates. By contrast, dopamine only stimulated cAMP formation by homogenates of day 0 and day 6 abdominal or ventral nerve cord. These results suggest that D1- and D2-like dopamine receptors of Manduca are regionally as well as temporally localized. AD - Department of Cell Biology and Anatomy, Campus Box 7090, Taylor Hall, University of North Carolina at Chapel Hill, NC 27599, USA. noelle@med.unc.edu FAU - Granger, N A AU - Granger NA FAU - Ebersohl, R AU - Ebersohl R FAU - Sparks, T C AU - Sparks TC LA - eng PT - Journal Article PL - ENGLAND TA - Insect Biochem Mol Biol JID - 9207282 RN - 0 (Dopamine Agonists) RN - 0 (Dopamine Antagonists) RN - 0 (Juvenile Hormones) RN - 0 (Quinolines) RN - 0 (Receptors, Dopamine) RN - 104-14-3 (Octopamine) RN - 16357-59-8 (EEDQ) RN - 2494-12-4 (N-acetyldopamine) RN - 50-67-9 (Serotonin) RN - 51-41-2 (Norepinephrine) RN - 51-61-6 (Dopamine) SB - IM MH - Animals MH - Brain/metabolism MH - Corpora Allata/drug effects/*metabolism MH - Dopamine/analogs & derivatives/pharmacology MH - Dopamine Agonists/pharmacology MH - Dopamine Antagonists/pharmacology MH - Juvenile Hormones/biosynthesis MH - Larva MH - Manduca/metabolism MH - Norepinephrine/pharmacology MH - Octopamine/pharmacology MH - Quinolines/pharmacology MH - Receptors, Dopamine/*metabolism MH - Research Support, Non-U.S. Gov't MH - Serotonin/pharmacology EDAT- 2000/07/06 11:00 MHDA- 2001/02/28 10:01 AID - S0965174800000473 [pii] PST - ppublish SO - Insect Biochem Mol Biol 2000 Aug-Sep;30(8-9):755-66. NR -------------------------------------------------------------------------------- 17: Gazi L et al. Cloning, expression, function...[PMID: 10832611] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 10832611 OWN - NLM STAT- MEDLINE DA - 20000816 DCOM- 20000816 LR - 20041204 PUBM- Print IS - 0028-1298 VI - 361 IP - 5 DP - 2000 May TI - Cloning, expression, functional coupling and pharmacological characterization of the rat dopamine D4 receptor. PG - 555-64 AB - It has been difficult to observe functional coupling of the D4 receptor to second messenger systems and a robust functional assay system for this receptor is still lacking. In the present study, the rat dopamine D4 receptor was cloned from rat retina. Sequence comparison revealed identity with the published sequence of Ashgari and co-workers, including the two amino acid insertions (V-Q) at position 92 which are not present in the published sequence of O'Malley and coworkers. The rat dopamine D4 receptor was stably expressed in Chinese hamster lung fibroblast CCL39 cells. [3H]spiperone saturation binding yielded a Bmax of 2,370+/-546 fmol/mg protein and a pKD of 8.74+/-0.14 (n=4). Forskolin-stimulated cAMP accumulation was inhibited by dopamine (Emax 61+/-1% inhibition of forskolin-stimulated levels, pEC50 7.33+/-0.06, n=23). A similar concentration-dependent inhibition was observed with the dopamine D2-like receptor agonists quinpirole and 7-OH-DPAT which elicited nearly the same Emax as dopamine. By contrast, apomorphine and a number of compounds with reported affinity for human dopamine D4 receptors (PD168077, U-101958, SDZ GLC 756, L-745,870 and NGD 94-1) behaved as partial agonists (Emax ranging between 26% and 56% of that of dopamine). The agonist effect of dopamine was completely blocked by preincubation with pertussis toxin, no further accumulation of cAMP above the forskolin-stimulated levels being observed. Antagonist pKB-values obtained against dopamine in this system were: 8.55+/-0.19 (n=3) for the partial agonist L-745,870, 8.38+/-0.23 (n=5) for spiperone, 7.18+/-0.17 (n=4) for haloperidol, 7.04+/-0.13 (n=4) for clozapine and <6 for raclopride. Other functional assays applicable were stimulation of [35S]GTPgammaS binding, extracellular acidification rate and a serum-responsive element using luciferase expression as a reporter gene. However, the receptor did not couple to phosphatidylinositol turnover or to intracellular Ca2+. Thus, expression of the rat dopamine D4 receptor in CCL39 cells provided several functional assay systems, of which inhibition of cAMP appeared to be the most robust one. These functional models can be used to evaluate the activity of compounds at the rat dopamine D4 receptor. AD - Nervous System Research, Novartis Pharma AG, Basel, Switzerland. FAU - Gazi, L AU - Gazi L FAU - Schoeffter, P AU - Schoeffter P FAU - Nunn, C AU - Nunn C FAU - Croskery, K AU - Croskery K FAU - Hoyer, D AU - Hoyer D FAU - Feuerbach, D AU - Feuerbach D LA - eng PT - Journal Article PL - GERMANY TA - Naunyn Schmiedebergs Arch Pharmacol JID - 0326264 RN - 0 (DNA, Complementary) RN - 0 (DNA-Binding Proteins) RN - 0 (Dopamine Agonists) RN - 0 (Dopamine Antagonists) RN - 0 (Inositol Phosphates) RN - 0 (Nuclear Proteins) RN - 0 (Receptors, Dopamine D2) RN - 0 (Serum Response Factor) RN - 0 (Sulfur Radioisotopes) RN - 0 (Virulence Factors, Bordetella) RN - 10028-17-8 (Tritium) RN - 137750-34-6 (receptors, dopamine D4) RN - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate)) RN - 51-61-6 (Dopamine) RN - 60-92-4 (Cyclic AMP) RN - 66428-89-5 (Forskolin) RN - 7440-70-2 (Calcium) RN - 749-02-0 (Spiperone) RN - EC 2.4.2.31 (Pertussis Toxin) SB - IM MH - Animals MH - Binding, Competitive MH - Calcium/metabolism MH - Cells, Cultured MH - Cloning, Molecular MH - Cyclic AMP/metabolism MH - DNA, Complementary/analysis MH - DNA-Binding Proteins/metabolism MH - Dopamine/*metabolism MH - Dopamine Agonists/pharmacology MH - Dopamine Antagonists/*pharmacology MH - Drug Interactions MH - Forskolin/pharmacology MH - Guanosine 5'-O-(3-Thiotriphosphate)/metabolism MH - Hamsters MH - Humans MH - Inositol Phosphates/metabolism MH - Nuclear Proteins/metabolism MH - Pertussis Toxin MH - Rats MH - Receptors, Dopamine D2/drug effects/genetics/*metabolism MH - Serum Response Factor MH - Spiperone/pharmacology MH - Sulfur Radioisotopes MH - Transfection MH - Tritium MH - Virulence Factors, Bordetella/pharmacology EDAT- 2000/06/01 09:00 MHDA- 2000/08/19 11:00 PST - ppublish SO - Naunyn Schmiedebergs Arch Pharmacol 2000 May;361(5):555-64. PR -------------------------------------------------------------------------------- 18: Ishiguro H et al. Association study between gen...[PMID: 10776673] Related Articles, Books, LinkOut PMID- 10776673 OWN - NLM STAT- MEDLINE DA - 20000612 DCOM- 20000612 LR - 20041204 PUBM- Print IS - 0145-6008 VI - 24 IP - 3 DP - 2000 Mar TI - Association study between genetic polymorphisms in the 14-3-3 eta chain and dopamine D4 receptor genes and alcoholism. PG - 343-7 AB - BACKGROUND: The dopaminergic system may be involved in the development of alcoholism. As part of our ongoing studies on the association between alcoholism and dopaminergic genes, we report herein a mutation analysis of the 14-3-3 eta chain gene (YWHAH) and an association study between alcoholism and the YWHAH and dopamine D4 receptor gene (DRD4) polymorphisms. METHODS: Nucleotide mutations were investigated using single-strand conformation polymorphism methods. Associations were analyzed using a case-control design involving 185 Japanese alcoholics and 286 Japanese controls. RESULTS: Five polymorphisms, -147G>A, -134(GCCTGCA)2-4, IVS1+31(G)7-8, IVS1+73-74ins(G), and 753A>G, were detected on the YWHAH, and three of them were novel. No significant associations were found between alcoholism and these polymorphisms or two additional polymorphisms on DRD4 exon III and DRD4 -521C/T. CONCLUSIONS: YWHAH and DRD4 do not appear to play a major role in the development of alcoholism. AD - Department of Medical Genetics, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan. FAU - Ishiguro, H AU - Ishiguro H FAU - Saito, T AU - Saito T FAU - Shibuya, H AU - Shibuya H FAU - Arinami, T AU - Arinami T LA - eng PT - Journal Article PL - UNITED STATES TA - Alcohol Clin Exp Res JID - 7707242 RN - 0 (14-3-3 Proteins) RN - 0 (Proteins) RN - 0 (Receptors, Dopamine D2) RN - 0 (YWHAH protein, human) RN - 137750-34-6 (receptors, dopamine D4) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) SB - IM MH - 14-3-3 Proteins MH - Adult MH - Aged MH - Alcoholism/*genetics MH - Case-Control Studies MH - Female MH - Humans MH - Male MH - Middle Aged MH - Mutation MH - Polymorphism, Genetic/*genetics MH - Proteins/*genetics MH - Receptors, Dopamine D2/*genetics MH - Research Support, Non-U.S. Gov't MH - *Tyrosine 3-Monooxygenase EDAT- 2000/04/25 09:00 MHDA- 2000/06/17 09:00 PST - ppublish SO - Alcohol Clin Exp Res 2000 Mar;24(3):343-7. DR -------------------------------------------------------------------------------- 19: Jovanovic V et al. Comparative pharmacological a...[PMID: 10591536] Related Articles, Compound via MeSH, Substance via MeSH, OMIM, Cited in PMC, Books, LinkOut PMID- 10591536 OWN - NLM STAT- MEDLINE DA - 20000106 DCOM- 20000106 LR - 20041204 PUBM- Print IS - 0960-314X VI - 9 IP - 5 DP - 1999 Oct TI - Comparative pharmacological and functional analysis of the human dopamine D4.2 and D4.10 receptor variants. PG - 561-8 AB - The human dopamine D4 receptor is a D2-like receptor which is a target for most common neuroleptics. Previous investigations have shown that this receptor displays a large polymorphic variation in the third intracellular loop involving a variable number of direct imperfect tandem repeats (VNTR) of 16 amino acids. The shortest and longest repeat variants reported to date contain two and 10 repeat units (D4.2 and D4.10). No major pharmacological differences have been reported for the most common variants of this receptor (D4.2, D4.4 and D4.7), although the D4.7 was reported by us to display a slightly lower potency for dopamine in functional assays. Direct pharmacological and functional comparison of the longest and shortest variants in this study suggest no major discrepancies in pharmacological or functional profile between both receptors. Both receptors display, on average, a 15-fold and 90-fold lower potency for epinephrine and norepinephrine, respectively, compared with dopamine. We observed small increases in functional potency and affinity for dopamine and quinpirole at the D4.10 receptor variant compared with the D4.2 receptor. Our data indicate that there is no direct relationship between the length of the polymorphism and changes in pharmacology or functional activity. These findings are a suitable caution against the arbitrary pooling of D4 receptor VNTR genotypes in genetic studies, based on length. AD - Laboratory of Molecular Neurobiology, Centre for Addiction and Mental Health, Clarke Division, and University of Toronto, Ontario, Canada. FAU - Jovanovic, V AU - Jovanovic V FAU - Guan, H C AU - Guan HC FAU - Van Tol, H H AU - Van Tol HH LA - eng PT - Journal Article PL - ENGLAND TA - Pharmacogenetics JID - 9211735 RN - 0 (Antipsychotic Agents) RN - 0 (Dopamine Agonists) RN - 0 (Receptors, Dopamine D2) RN - 0 (Recombinant Proteins) RN - 137750-34-6 (receptors, dopamine D4) RN - 51-41-2 (Norepinephrine) RN - 51-43-4 (Epinephrine) RN - 51-61-6 (Dopamine) RN - 85760-74-3 (Quinpirole) SB - IM MH - Amino Acid Sequence MH - Animals MH - Antipsychotic Agents/pharmacology MH - Binding, Competitive MH - CHO Cells MH - Comparative Study MH - Dopamine/metabolism/pharmacology MH - Dopamine Agonists/metabolism MH - Epinephrine/pharmacology MH - Hamsters MH - Humans MH - Minisatellite Repeats MH - Models, Molecular MH - Molecular Sequence Data MH - Norepinephrine/pharmacology MH - Pharmacogenetics MH - Polymorphism, Genetic MH - Quinpirole/metabolism MH - Receptors, Dopamine D2/*drug effects/*genetics/metabolism MH - Recombinant Proteins/chemistry/genetics/metabolism MH - Research Support, Non-U.S. Gov't MH - *Variation (Genetics) EDAT- 1999/12/11 MHDA- 1999/12/11 00:01 PST - ppublish SO - Pharmacogenetics 1999 Oct;9(5):561-8. PR -------------------------------------------------------------------------------- 20: Hill SY et al. Linkage studies of D2 and D4 ...[PMID: 10581489] Related Articles, Books, LinkOut PMID- 10581489 OWN - NLM STAT- MEDLINE DA - 20000224 DCOM- 20000224 LR - 20041204 PUBM- Print IS - 0148-7299 VI - 88 IP - 6 DP - 1999 Dec 15 TI - Linkage studies of D2 and D4 receptor genes and alcoholism. PG - 676-85 AB - The purpose of the present study was to evaluate two polymorphisms near the D2 receptor gene (TaqI A RFLP and C microsatellite) and a VNTR for D4. A nonparametric linkage (NPL) technique, SIBPAL, was used to test for the presence or absence of linkage in 54 multiplex alcoholic families. These families had been ascertained through two alcoholic proband siblings in order to increase the density of alcoholic cases within these pedigrees. Phenotypic definitions of alcoholism were manipulated in an effort to determine the impact of severity (signs of physical dependence, early age of onset, presence of antisocial personality disorder) on the likelihood of finding positive evidence for linkage. A regression analysis that simultaneously evaluated the allele sharing identical by descent for Feighner criteria alcoholism in affected, unaffected, and discordant sib pairs (SIBPAL) for two D2 polymorphisms and the D4 polymorphism gave no evidence for linkage. Phenotypes associated with greater alcoholism severity (presence of physical dependence symptoms, earlier onset, or comorbid antisocial personality disorder) revealed some evidence for linkage. The presence of one or more physical dependence symptoms in combination with Feighner criteria alcoholism provided some evidence favoring linkage (TaqI A and D4). Alcoholics with an earlier onset of alcoholism showed some evidence for linkage especially when the presence of physical dependence was required (e. g., morning drinking, wanted to stop drinking but could not, binges or benders, and evidence of withdrawal symptoms). Finally, alcoholics with antisocial personality disorder differed significantly in their allele sharing from nonalcoholics for both D2 polymorphisms. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:676-685, 1999. CI - Copyright 1999 Wiley-Liss, Inc. AD - Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. FAU - Hill, S Y AU - Hill SY FAU - Zezza, N AU - Zezza N FAU - Wipprecht, G AU - Wipprecht G FAU - Xu, J AU - Xu J FAU - Neiswanger, K AU - Neiswanger K LA - eng GR - AA05909-15/AA/NIAAA GR - AA0808208/AA/NIAAA GR - AA11304-02/AA/NIAAA GR - etc. PT - Journal Article PL - UNITED STATES TA - Am J Med Genet JID - 7708900 RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) SB - IM MH - Adolescent MH - Adult MH - Age of Onset MH - Alcohol-Induced Disorders, Nervous System/genetics MH - Alcoholism/diagnosis/*genetics MH - Antisocial Personality Disorder/genetics MH - Female MH - Genetic Predisposition to Disease/*genetics MH - Genotype MH - Humans MH - Linkage (Genetics)/*genetics MH - Male MH - Middle Aged MH - Nuclear Family MH - Phenotype MH - Polymorphism, Genetic/*genetics MH - Quantitative Trait, Heritable MH - Receptors, Dopamine D2/*genetics MH - Research Support, U.S. Gov't, P.H.S. MH - Sex Factors MH - Statistics EDAT- 1999/12/03 09:00 MHDA- 2000/02/26 09:00 AID - 10.1002/(SICI)1096-8628(19991215)88:6<676::AID-AJMG18>3.0.CO;2-S [pii] PST - ppublish SO - Am J Med Genet 1999 Dec 15;88(6):676-85. DR -------------------------------------------------------------------------------- 21: Hill SY et al. Personality traits and dopami...[PMID: 10581482] Related Articles, Books, LinkOut PMID- 10581482 OWN - NLM STAT- MEDLINE DA - 20000224 DCOM- 20000224 LR - 20050119 PUBM- Print IS - 0148-7299 VI - 88 IP - 6 DP - 1999 Dec 15 TI - Personality traits and dopamine receptors (D2 and D4): linkage studies in families of alcoholics. PG - 634-41 AB - Activation of the mesolimbic dopamine pathway appears to promote drug- and alcohol-seeking behavior in laboratory animals. Results for association and linkage analysis between various alcohol dependence phenotypes and the dopamine receptors have been quite mixed. Similarly, both positive and negative results have been presented concerning dopamine receptor genes and temperament. Cloninger has postulated that the novelty seeking factor from the Tridimensional Personality Questionnaire (TPQ) may be related to the dopamine neurotransmitter system. As novelty seeking is a trait of some importance for substance-dependent individuals, our goal was to test this relationship within a sample of families of alcoholics. No evidence favoring linkage between D2, D4, or DAT1 was found for TPQ novelty seeking. However, the harm-avoidance trait from the TPQ showed evidence for linkage to both the D4 and one of the D2 loci (TaqI A). The Multidimensional Personality Questionnaire (MPQ) was used to provide converging evidence for these results. The TPQ harm-avoidance scale loads heavily on introversion (worry, pessimism, shyness), characteristics that may be especially salient in alcoholic families. Thus, planned comparisons were made between selected MPQ traits measuring the affective dimension (negative affectivity, stress reaction, alienation, and well-being). We find evidence favoring linkage between the D2 and D4 receptor loci and these MPQ traits, with stronger evidence being seen for the D2 polymorphisms. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:634-641, 1999. CI - Copyright 1999 Wiley-Liss, Inc. AD - Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. FAU - Hill, S Y AU - Hill SY FAU - Zezza, N AU - Zezza N FAU - Wipprecht, G AU - Wipprecht G FAU - Locke, J AU - Locke J FAU - Neiswanger, K AU - Neiswanger K LA - eng GR - AA05909-15/AA/NIAAA GR - AA0808208/AA/NIAAA GR - AA11304-02/AA/NIAAA GR - etc. PT - Journal Article PL - UNITED STATES TA - Am J Med Genet JID - 7708900 RN - 0 (Carrier Proteins) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Receptors, Dopamine D2) RN - 0 (dopamine transporter proteins) RN - 137750-34-6 (receptors, dopamine D4) SB - IM MH - Adolescent MH - Age of Onset MH - Aggression MH - Alcoholism/*genetics/psychology MH - Anxiety/genetics MH - Avoidance Learning MH - Carrier Proteins/genetics MH - Exploratory Behavior MH - Family Health MH - Female MH - Genetic Predisposition to Disease MH - Humans MH - *Linkage (Genetics) MH - Male MH - *Membrane Glycoproteins MH - *Membrane Transport Proteins MH - *Nerve Tissue Proteins MH - Personality/*genetics MH - Polymorphism, Genetic/genetics MH - *Quantitative Trait, Heritable MH - Receptors, Dopamine D2/*genetics MH - Research Support, U.S. Gov't, P.H.S. MH - Reward MH - Social Alienation MH - Stress, Psychological/genetics EDAT- 1999/12/03 09:00 MHDA- 2000/02/26 09:00 AID - 10.1002/(SICI)1096-8628(19991215)88:6<634::AID-AJMG11>3.0.CO;2-M [pii] PST - ppublish SO - Am J Med Genet 1999 Dec 15;88(6):634-41. DR -------------------------------------------------------------------------------- 22: Bau CH et al. Dopamine D4 receptor gene and...[PMID: 10551544] Related Articles, Books, LinkOut PMID- 10551544 OWN - NLM STAT- MEDLINE DA - 19991202 DCOM- 19991202 LR - 20041204 PUBM- Print IS - 0955-8829 VI - 9 IP - 3 DP - 1999 Sep TI - Dopamine D4 receptor gene and personality dimensions in Brazilian male alcoholics. PG - 139-43 AB - The presence of the seven-repeat allele of the VNTR in the exon 3 of the dopamine D4 receptor gene (DRD4) has been associated in healthy subjects to the personality trait of novelty seeking. The present study focuses these observations on a sample of Brazilian male alcoholics, evaluated on the temperament dimensions originally described by Cloninger. The genotypes observed are in agreement with those expected under Hardy-Weinberg equilibrium. Subjects with the seven-repeat allele manifest lower harm avoidance scores. No significant differences between subjects with or without the seven-repeat allele in the scores of novelty seeking or reward dependence were observed. The lack of association between novelty seeking and the DRD4 exon 3 polymorphism is further corroborated by the fact that the comorbid antisocial personality disorder is not associated to the presence of the seven-repeat allele. These results could be explained by a biological connection between the personality dimensions of novelty seeking and harm avoidance. AD - Departamento de Genetica, Instituto de Biociencias, Porto Alegre, RS, Brazil. bau@if.ufrgs.br FAU - Bau, C H AU - Bau CH FAU - Roman, T AU - Roman T FAU - Almeida, S AU - Almeida S FAU - Hutz, M H AU - Hutz MH LA - eng PT - Journal Article PL - ENGLAND TA - Psychiatr Genet JID - 9106748 RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) SB - IM MH - Adult MH - Alcoholism/*genetics/*psychology MH - Brazil MH - Chi-Square Distribution MH - European Continental Ancestry Group/genetics MH - Exons MH - Genotype MH - Humans MH - Male MH - Middle Aged MH - *Minisatellite Repeats MH - Personality/*genetics MH - Polymerase Chain Reaction MH - Receptors, Dopamine D2/*genetics MH - Research Support, Non-U.S. Gov't EDAT- 1999/11/07 MHDA- 1999/11/07 00:01 PST - ppublish SO - Psychiatr Genet 1999 Sep;9(3):139-43. DR -------------------------------------------------------------------------------- 23: Parsian A et al. Human chromosomes 11p15 and 4...[PMID: 10490712] Related Articles, Books, LinkOut PMID- 10490712 OWN - NLM STAT- MEDLINE DA - 19991117 DCOM- 19991117 LR - 20041117 PUBM- Print IS - 0148-7299 VI - 88 IP - 5 DP - 1999 Oct 15 TI - Human chromosomes 11p15 and 4p12 and alcohol dependence: possible association with the GABRB1 gene. PG - 533-8 AB - To determine the role of genes in the chromosomal regions 11p15 and 4p12 in the development of alcohol dependence, a sample of alcoholics (n = 133) and normal controls (n = 89) were screened using polymorphisms in the dopamine D4 receptor (DRD4), tyrosine hydroxylase (TH), and GABA receptor beta1 (GABRbeta1) genes. Comparison of total alcoholics with normal controls for GABRbeta1 gene was highly significant (p = 0.004). The difference between type II alcoholics and normal controls for the same allele frequencies was also significant (p = 0.029). The allele distributions of the polymorphisms in the DRD4 and TH genes in alcoholics and normal controls were similar and their differences were not significant. Our association studies indicate that the GABRbeta1 gene may play a role in the development of alcoholism. Therefore, it is important to screen a sample of well-characterized alcoholics with functional polymorphisms in all of the GABAalpha receptor subunit genes and determine their relationship with alcoholism phenotypes. Results with TH and DRD4 genes indicate that these two genes may not play major roles in the development of alcoholism. AD - Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. FAU - Parsian, A AU - Parsian A FAU - Zhang, Z H AU - Zhang ZH LA - eng GR - AA09515/AA/NIAAA GR - MH31302/MH/NIMH PT - Journal Article PL - UNITED STATES TA - Am J Med Genet JID - 7708900 RN - 0 (Receptors, GABA-B) SB - IM MH - Alcoholism/*genetics MH - Alleles MH - Antisocial Personality Disorder/genetics MH - Case-Control Studies MH - *Chromosomes, Human, Pair 11 MH - *Chromosomes, Human, Pair 4 MH - Female MH - Gene Frequency MH - Haplotypes MH - Humans MH - Introns MH - Linkage Disequilibrium MH - Male MH - Phenotype MH - Polymorphism, Genetic MH - Receptors, GABA-B/*genetics MH - Research Support, U.S. Gov't, P.H.S. MH - Risk Factors EDAT- 1999/09/22 MHDA- 1999/09/22 00:01 AID - 10.1002/(SICI)1096-8628(19991015)88:5<533::AID-AJMG18>3.0.CO;2-C [pii] PST - ppublish SO - Am J Med Genet 1999 Oct 15;88(5):533-8. DR -------------------------------------------------------------------------------- 24: Thrasher MJ et al. Clozapine's effects on ethano...[PMID: 10470981] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 10470981 OWN - NLM STAT- MEDLINE DA - 19991026 DCOM- 19991026 LR - 20041204 PUBM- Print IS - 0145-6008 VI - 23 IP - 8 DP - 1999 Aug TI - Clozapine's effects on ethanol's motivational properties. PG - 1377-85 AB - BACKGROUND: Although dopamine D1 and D2 receptors have been implicated in ethanol's motivational effects, little is known about the contribution of dopamine D4 receptors. The present experiments examined the effects of clozapine, a dopamine D4 receptor antagonist, on ethanol's aversive, rewarding, stimulant, and reinforcing properties. METHODS: For taste conditioning, adult male Swiss-Webster mice received five conditioning trials consisting of 1-hr access to 0.2 M NaCl. After NaCl access on trials 1-4, subjects received clozapine (0, 1, or 2 mg/kg) followed 30 min later by 0, 2, or 4 g/kg ethanol. For place conditioning, Swiss-Webster mice received six pairings of a tactile stimulus with ethanol (2 g/kg, intraperitoneally), clozapine (1 mg/kg, intraperitoneally) + ethanol, or clozapine alone. Locomotor activity in a 30-min test was determined in Swiss-Webster mice receiving 0, 0.5, or 1.0 mg/kg clozapine and 0, 1, or 2 g/kg ethanol. In a drinking study, separate groups of adult male C57BL/6J mice were allowed 30-min access to either 10% v/v ethanol mixed in 10% w/v sucrose or 10% sucrose without ethanol. During testing, both groups were given 0 or 1 mg/kg clozapine 30 min before fluid access. RESULTS: Ethanol flavor pairings during taste conditioning reduced subsequent flavor intakes, indicating the development of conditioned taste aversion. Clozapine reduced the magnitude of 4 g/kg ethanol-conditioned aversion only on trial 4 at the 2 mg/kg dose. Conditioned place preference for the ethanol-paired stimulus was not altered by clozapine. Clozapine alone did not produce either conditioned preference or aversion. Ethanol-stimulated activity was reduced by clozapine treatment. However, clozapine alone did not alter locomotor activity levels. Clozapine reduced sucrose consumption but did not alter ethanol/sucrose intake. CONCLUSIONS: These data suggest that clozapine influences a limited range of ethanol-motivated behaviors. Specifically, dopamine D4 receptors appear important for ethanol's stimulant effect and possibly ethanol aversion, but not ethanol reward and reinforcement. AD - Department of Behavioral Neuroscience, Portland Alcohol Research Center, Oregon Health Sciences University 97201-3098, USA. FAU - Thrasher, M J AU - Thrasher MJ FAU - Freeman, P A AU - Freeman PA FAU - Risinger, F O AU - Risinger FO LA - eng GR - AA07468/AA/NIAAA GR - AA10520/AA/NIAAA GR - AA10760/AA/NIAAA PT - Journal Article PL - UNITED STATES TA - Alcohol Clin Exp Res JID - 7707242 RN - 0 (Central Nervous System Depressants) RN - 0 (Dopamine Antagonists) RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) RN - 5786-21-0 (Clozapine) RN - 64-17-5 (Ethanol) SB - IM MH - Alcohol Drinking/psychology MH - Animals MH - Central Nervous System Depressants/*administration & dosage MH - Clozapine/*administration & dosage MH - Conditioning (Psychology)/drug effects MH - Dopamine Antagonists/*administration & dosage MH - Ethanol/*administration & dosage MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Motor Activity/drug effects MH - Receptors, Dopamine D2/antagonists & inhibitors/*drug effects/physiology MH - Research Support, U.S. Gov't, P.H.S. EDAT- 1999/09/02 MHDA- 1999/09/02 00:01 AID - 00000374-199908000-00012 [pii] PST - ppublish SO - Alcohol Clin Exp Res 1999 Aug;23(8):1377-85. DR -------------------------------------------------------------------------------- 25: Anokhina IP et al. [Hereditary alcoholism: some ...[PMID: 10432864] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 10432864 OWN - NLM STAT- MEDLINE DA - 19990831 DCOM- 19990831 LR - 20041204 PUBM- Print IS - 0869-6047 IP - 6 DP - 1999 TI - [Hereditary alcoholism: some neurochemical and genetic mechanisms] PG - 43-7 FAU - Anokhina, I P AU - Anokhina IP FAU - Vertinskaia, A G AU - Vertinskaia AG FAU - Vekshina, N L AU - Vekshina NL FAU - Nebarakova, T P AU - Nebarakova TP FAU - Ovchinnikov, I V AU - Ovchinnikov IV FAU - Druzhina, E V AU - Druzhina EV FAU - Ovchinnikova, O I AU - Ovchinnikova OI LA - rus PT - Journal Article TT - Nasledstvennyi alkogolizm: nekotorye neirokhimicheskie i geneticheskie mekhanizmy. PL - RUSSIA TA - Vestn Ross Akad Med Nauk JID - 9215641 RN - 0 (Genetic Markers) RN - 0 (Receptors, Dopamine D2) RN - 102-32-9 (3,4-Dihydroxyphenylacetic Acid) RN - 137750-34-6 (receptors, dopamine D4) RN - 51-41-2 (Norepinephrine) RN - 63-84-3 (Dihydroxyphenylalanine) RN - 9007-49-2 (DNA) SB - IM MH - 3,4-Dihydroxyphenylacetic Acid/blood MH - Alcoholism/blood/*genetics MH - Alleles MH - Brain/*metabolism MH - Comparative Study MH - DNA/*biosynthesis MH - Dihydroxyphenylalanine/blood MH - *Genetic Diseases, Inborn/blood/genetics MH - Genetic Markers MH - Genetic Predisposition to Disease MH - Genotype MH - Humans MH - Male MH - Minisatellite Repeats MH - Norepinephrine/blood MH - Receptors, Dopamine D2/biosynthesis/*genetics EDAT- 1999/08/05 MHDA- 1999/08/05 00:01 PST - ppublish SO - Vestn Ross Akad Med Nauk 1999;(6):43-7. DR -------------------------------------------------------------------------------- 26: Paterson AD et al. Dopamine D4 receptor gene: no...[PMID: 10379515] Related Articles, Cited in PMC, Books, LinkOut PMID- 10379515 OWN - NLM STAT- MEDLINE DA - 19990901 DCOM- 19990901 LR - 20041204 PUBM- Print IS - 0893-133X VI - 21 IP - 1 DP - 1999 Jul TI - Dopamine D4 receptor gene: novelty or nonsense? PG - 3-16 AB - Although the role of genetics in personality has been studied extensively at a phenomenological level, only lately has the investigation of specific genes been performed. Recent reports suggest that DNA variants of the dopamine D4 receptor gene (DRD4) are associated with the personality trait of novelty seeking; however, others fail to replicate this finding. Such conflicting results suggest either a weak effect, an association only in certain populations, or a false-positive resulting from population stratification. We provide a critical analysis of genetic studies of DRD4 variants with novelty seeking, alcoholism, drug abuse, and attention deficit hyperactivity disorder. Evidence for the role of DRD4 in novelty seeking is inconclusive, with a number of methodological concerns. Use of more conservative statistical criteria for significance, employing gene haplotypes, as well as linkage disequilibrium studies, are recommended. The molecular biology of the D4 gene is also reviewed. AD - Department of Psychiatry, University of Toronto, Ontario, Canada. FAU - Paterson, A D AU - Paterson AD FAU - Sunohara, G A AU - Sunohara GA FAU - Kennedy, J L AU - Kennedy JL LA - eng PT - Journal Article PT - Review PT - Review, Tutorial PL - UNITED STATES TA - Neuropsychopharmacology JID - 8904907 RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) SB - IM MH - Exploratory Behavior/*physiology MH - Humans MH - Personality/*genetics MH - Polymorphism, Genetic MH - Receptors, Dopamine D2/*genetics/metabolism MH - Research Support, Non-U.S. Gov't RF - 90 EDAT- 1999/06/24 MHDA- 1999/06/24 00:01 AID - S0893133X98001158 [pii] AID - 10.1016/S0893-133X(98)00115-8 [doi] PST - ppublish SO - Neuropsychopharmacology 1999 Jul;21(1):3-16. DR -------------------------------------------------------------------------------- 27: Giuffrida A et al. Dopamine activation of endoge...[PMID: 10204543] Related Articles, Compound via MeSH, Substance via MeSH, Cited in PMC, Books, LinkOut PMID- 10204543 OWN - NLM STAT- MEDLINE DA - 19990430 DCOM- 19990430 LR - 20041117 PUBM- Print IS - 1097-6256 VI - 2 IP - 4 DP - 1999 Apr TI - Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. PG - 358-63 AB - We measured endogenous cannabinoid release in dorsal striatum of freely moving rats by microdialysis and gas chromatography/mass spectrometry. Neural activity stimulated the release of anandamide, but not of other endogenous cannabinoids such as 2-arachidonylglycerol. Moreover, anandamide release was increased eightfold over baseline after local administration of the D2-like (D2, D3, D4) dopamine receptor agonist quinpirole, a response that was prevented by the D2-like receptor antagonist raclopride. Administration of the D1-like (D1, D5) receptor agonist SKF38393 had no such effect. These results suggest that functional interactions between endocannabinoid and dopaminergic systems may contribute to striatal signaling. In agreement with this hypothesis, pretreatment with the cannabinoid antagonist SR141716A enhanced the stimulation of motor behavior elicited by systemic administration of quinpirole. The endocannabinoid system therefore may act as an inhibitory feedback mechanism countering dopamine-induced facilitation of motor activity. AD - Department of Pharmacology, University of California at Irvine, 92697-4625, USA. FAU - Giuffrida, A AU - Giuffrida A FAU - Parsons, L H AU - Parsons LH FAU - Kerr, T M AU - Kerr TM FAU - Rodriguez de Fonseca, F AU - Rodriguez de Fonseca F FAU - Navarro, M AU - Navarro M FAU - Piomelli, D AU - Piomelli D LA - eng GR - DA12413/DA/NIDA GR - DA12447/DA/NIDA PT - Journal Article PL - UNITED STATES TA - Nat Neurosci JID - 9809671 RN - 0 (Arachidonic Acids) RN - 0 (Dopamine Agonists) RN - 0 (Dopamine Antagonists) RN - 0 (Endocannabinoids) RN - 0 (Ethanolamines) RN - 0 (Glycerides) RN - 0 (Palmitic Acids) RN - 0 (Piperidines) RN - 0 (Pyrazoles) RN - 0 (Receptors, Cannabinoid) RN - 0 (Receptors, Dopamine D2) RN - 0 (Receptors, Drug) RN - 0 (Salicylamides) RN - 111-58-0 (N-oleoylethanolamine) RN - 158681-13-1 (SR 141716A) RN - 4368-28-9 (Tetrodotoxin) RN - 51-61-6 (Dopamine) RN - 53847-30-6 (2-arachidonylglycerol) RN - 544-31-0 (palmidrol) RN - 67287-49-4 (2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine) RN - 7440-09-7 (Potassium) RN - 7440-23-5 (Sodium) RN - 7440-70-2 (Calcium) RN - 84225-95-6 (Raclopride) RN - 85760-74-3 (Quinpirole) RN - 94421-68-8 (anandamide) SB - IM CIN - Nat Neurosci. 1999 Apr;2(4):303-4. PMID: 10204533 MH - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology MH - Animals MH - Arachidonic Acids/*secretion MH - Calcium/pharmacology MH - Corpus Striatum/*drug effects/physiology/secretion MH - Dopamine/*pharmacology MH - Dopamine Agonists/pharmacology MH - Dopamine Antagonists/pharmacology MH - Endocannabinoids MH - Ethanolamines/pharmacology MH - Glycerides/pharmacology MH - Hyperkinesis/chemically induced MH - Male MH - Mass Fragmentography MH - Microdialysis MH - Motor Activity/drug effects/*physiology MH - Palmitic Acids/pharmacology MH - Piperidines/pharmacology MH - Potassium/*pharmacology MH - Pyrazoles/pharmacology MH - Quinpirole/pharmacology MH - Raclopride MH - Rats MH - Rats, Wistar MH - Receptors, Cannabinoid MH - Receptors, Dopamine D2/*drug effects/physiology MH - Receptors, Drug/*drug effects/physiology MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, P.H.S. MH - Salicylamides/pharmacology MH - Signal Transduction/*drug effects/physiology MH - Single-Blind Method MH - Sodium/physiology MH - Tetrodotoxin/pharmacology EDAT- 1999/04/16 02:03 MHDA- 2001/03/23 10:01 AID - 10.1038/7268 [doi] PST - ppublish SO - Nat Neurosci 1999 Apr;2(4):358-63. NR -------------------------------------------------------------------------------- 28: Noda-Saita K et al. Dopamine D4-like binding site...[PMID: 10049714] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 10049714 OWN - NLM STAT- MEDLINE DA - 19990311 DCOM- 19990311 LR - 20041204 PUBM- Print IS - 0006-291X VI - 255 IP - 2 DP - 1999 Feb 16 TI - Dopamine D4-like binding sites labeled by [3H]nemonapride include substantial serotonin 5-HT2A receptors in primate cerebral cortex. PG - 367-70 AB - Dopamine D4-like binding sites are abundant in human cerebral cortex as detected by [3H]nemonapride. The extremely low density of D4 mRNA in human cerebral cortex is inconsistent with the high amount of D4-like binding sites. To investigate the nature of the D4-like receptors, [3H]nemonapride binding sites in the nonhuman primate cerebral cortex were characterized. Although [3H]nemonapride binding sites were D4-like, displaceable by clozapine but not raclopride, [3H]nemonapride binding was not displaced by selective D4 antagonists but was displaced by the selective 5-HT2A antagonist MDL100907. Using [3H]ketanserin as a 5-HT2A ligand, nemonapride showed high affinity for monkey (Ki = 10.4 nM) and cloned human (Ki = 9.4 nM) 5-HT2A receptors, while its affinity for rat receptors was lower (Ki = 140 nM). The present study demonstrates that cerebral cortical D4-like binding sites labeled by [3H]nemonapride in nonhuman primates consist of a very small portion of D4, but a substantial portion of 5-HT2A receptors. The unexpectedly high affinity of nemonapride for primate 5-HT2A receptor suggests reconsidering previous data from other studies using [3H]nemonapride, particularly those on D4-like receptors. CI - Copyright 1999 Academic Press. AD - Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan. FAU - Noda-Saita, K AU - Noda-Saita K FAU - Matsumoto, M AU - Matsumoto M FAU - Hidaka, K AU - Hidaka K FAU - Hatanaka, K AU - Hatanaka K FAU - Ohmori, J AU - Ohmori J FAU - Okada, M AU - Okada M FAU - Yamaguchi, T AU - Yamaguchi T LA - eng PT - Journal Article PL - UNITED STATES TA - Biochem Biophys Res Commun JID - 0372516 RN - 0 ((R)-5-chloro-4-cyclopropylcarbonylamino-2-methoxy-N-(1-(3-methoxybenzyl)- 3-pyrrolidinyl)benzamide monooxalate) RN - 0 (Anisoles) RN - 0 (Benzamides) RN - 0 (Dopamine Antagonists) RN - 0 (Ligands) RN - 0 (Piperazines) RN - 0 (Propylamines) RN - 0 (Receptor, Serotonin, 5-HT2A) RN - 0 (Receptors, Dopamine D2) RN - 0 (Receptors, Serotonin) RN - 0 (Sulfonamides) RN - 10028-17-8 (Tritium) RN - 13523-86-9 (Pindolol) RN - 137750-34-6 (receptors, dopamine D4) RN - 149409-57-4 (N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride) RN - 170858-33-0 (U 101387) RN - 70325-83-6 (nemonapride) RN - 74050-98-9 (Ketanserin) SB - IM MH - Animals MH - Anisoles/pharmacology MH - Benzamides/*metabolism/pharmacology MH - Binding Sites/drug effects MH - Cerebral Cortex/drug effects/*metabolism MH - Dopamine Antagonists/metabolism MH - Humans MH - Ketanserin/metabolism/pharmacology MH - Ligands MH - Macaca fascicularis MH - Pindolol/pharmacology MH - Piperazines/pharmacology MH - Propylamines/pharmacology MH - Receptor, Serotonin, 5-HT2A MH - Receptors, Dopamine D2/antagonists & inhibitors/*metabolism MH - Receptors, Serotonin/*metabolism MH - Sulfonamides/pharmacology MH - Tritium EDAT- 1999/03/02 MHDA- 1999/03/02 00:01 AID - S0006291X99902206 [pii] PST - ppublish SO - Biochem Biophys Res Commun 1999 Feb 16;255(2):367-70. NR -------------------------------------------------------------------------------- 29: Belliotti TR et al. Isoindolinone enantiomers hav...[PMID: 9873377] Related Articles, Books, LinkOut PMID- 9873377 OWN - NLM STAT- MEDLINE DA - 19990201 DCOM- 19990201 LR - 20041204 PUBM- Print IS - 0960-894X VI - 8 IP - 12 DP - 1998 Jun 16 TI - Isoindolinone enantiomers having affinity for the dopamine D4 receptor. PG - 1499-502 AB - PD 108635 (1) was identified as a potent dopamine D4 ligand and we wanted to replace the benzylic alcohol with a metabolically more stable moiety. Investigations led to the discovery of a series of isoindolinones having D4 affinity. AD - Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, MI 48105, USA. FAU - Belliotti, T R AU - Belliotti TR FAU - Brink, W A AU - Brink WA FAU - Kesten, S R AU - Kesten SR FAU - Rubin, J R AU - Rubin JR FAU - Wustrow, D J AU - Wustrow DJ FAU - Zoski, K T AU - Zoski KT FAU - Whetzel, S Z AU - Whetzel SZ FAU - Corbin, A E AU - Corbin AE FAU - Pugsley, T A AU - Pugsley TA FAU - Heffner, T G AU - Heffner TG FAU - Wise, L D AU - Wise LD LA - eng PT - Journal Article PL - ENGLAND TA - Bioorg Med Chem Lett JID - 9107377 RN - 0 (Indoles) RN - 0 (Receptors, Dopamine D2) RN - 0 (Receptors, Serotonin) RN - 137750-34-6 (receptors, dopamine D4) SB - IM MH - Animals MH - Indoles/*chemistry/*pharmacology MH - Motor Activity/drug effects MH - Rats MH - Receptors, Dopamine D2/*drug effects MH - Receptors, Serotonin/metabolism MH - Stereoisomerism MH - Structure-Activity Relationship MH - X-Ray Diffraction EDAT- 1999/01/05 MHDA- 1999/01/05 00:01 AID - S0960894X98002522 [pii] PST - ppublish SO - Bioorg Med Chem Lett 1998 Jun 16;8(12):1499-502. NR -------------------------------------------------------------------------------- 30: Drago J et al. Dopamine receptors and dopami...[PMID: 9691193] Related Articles, Cited in PMC, Books, LinkOut PMID- 9691193 OWN - NLM STAT- MEDLINE DA - 19980911 DCOM- 19980911 LR - 20050119 PUBM- Print IS - 0378-5866 VI - 20 IP - 2-3 DP - 1998 TI - Dopamine receptors and dopamine transporter in brain function and addictive behaviors: insights from targeted mouse mutants. PG - 188-203 AB - Recent advances in molecular biology have resulted in a number of genetically manipulated mice with defined changes at dopamine receptor and the dopamine transporter (DAT) loci. Mice with targeted mutations at the D1 receptor (D1R) are growth-retarded and show downregulated expression of dynorphin and substance P. Behavioral assessment indicates that mutants have deficiencies in spatial learning and initiating movement, as well as in responding to novel stimuli. D1R mutants do not become locomotor activated with cocaine or show upregulated immediate early gene (IEG) expression, but D2 receptor-dependent IEG changes are intact. Acute cocaine administration increases substance P levels, suggesting that striatal expression of this neuropeptide can be modulated by D1R-independent processes. Failure of locomotor activation is also seen with repeated amphetamine treatment. Surprisingly, D1R-deficient mice retain cocaine-conditioned place preference. In contrast, D2 receptor knockout mice are bradykinetic, show increased striatal enkephalin expression and an absence of opiate rewarding effects. D3 receptor mutants are hyperactive when assessed in an exploratory assay and display reduced anxiety-associated behavior in an elevated plus maze test. The recently described D4 receptor homozygous mutants exhibit a reduction in baseline locomotor activity and were shown to be supersensitive to the locomotor activating effects of alcohol and psychostimulant drugs. As expected, DAT knockout mice are hyperactive and do not respond to cocaine or amphetamine. The observation that D2 and D4 dopamine receptor and DAT mutants show compensatory effects, together with the complicating issue of their hybrid genetic background may temper conclusions regarding the direct effects of the targeted mutation on phenotype. AD - Department of Anatomy, Monash University, Clayton, Australia. John.Drago@med.monash.edu.au FAU - Drago, J AU - Drago J FAU - Padungchaichot, P AU - Padungchaichot P FAU - Accili, D AU - Accili D FAU - Fuchs, S AU - Fuchs S LA - eng PT - Journal Article PT - Review PT - Review, Tutorial PL - SWITZERLAND TA - Dev Neurosci JID - 7809375 RN - 0 (Carrier Proteins) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Receptors, Dopamine) RN - 0 (dopamine transporter proteins) SB - IM MH - Animals MH - Behavior, Addictive/*physiopathology MH - Brain/*physiology MH - Carrier Proteins/*physiology MH - Gene Targeting MH - *Membrane Glycoproteins MH - *Membrane Transport Proteins MH - Mice MH - Mutation/physiology MH - *Nerve Tissue Proteins MH - Receptors, Dopamine/*physiology MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, Non-P.H.S. RF - 133 EDAT- 1998/08/06 02:01 MHDA- 2000/08/16 11:00 AID - dne20188 [pii] PST - ppublish SO - Dev Neurosci 1998;20(2-3):188-203. DR -------------------------------------------------------------------------------- 31: Li L et al. Dopamine inhibits vasopressin...[PMID: 9689005] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 9689005 OWN - NLM STAT- MEDLINE DA - 19980827 DCOM- 19980827 LR - 20041204 PUBM- Print IS - 0002-9513 VI - 275 IP - 1 Pt 2 DP - 1998 Jul TI - Dopamine inhibits vasopressin-dependent cAMP production in the rat cortical collecting duct. PG - F62-7 AB - Dopamine inhibits Na+ and water reabsorption in the rat cortical collecting duct (CCD) in the presence of arginine vasopressin (AVP). This inhibition appears to involve the D4 dopamine receptor isoform, which inhibits cAMP production; however, the D1A receptor, which stimulates cAMP production, is also expressed in the CCD. To discriminate between these opposing effects, we measured cAMP production in intact CCD segments. The basal rate of cAMP production ranged from 6.5 to 10 fmol/mm of tubule length over a 7-min incubation period, and it was unaffected by either dopamine or the D1A-specific agonist fenoldopam. AVP increased cAMP production to the range of 85-153 fmol . mm-1 . 7 min-1. Whereas neither 0.1 nor 1.0 microM fenoldopam affected AVP-dependent cAMP production, dopamine reduced it in a dose-dependent manner, achieving a maximum inhibition of 50% at 10 microM. This effect was reversed by the D4 receptor antagonist clozapine but not by pimozide or spiperone (antagonists of D2 and D3 receptors) or by calphostin C or chelerythrine (inhibitors of protein kinase C). We conclude that dopamine inhibits transepithelial Na+ transport and osmotic water permeability in the presence of AVP by inhibition of cAMP production, which is mediated by the D4 receptor isoform linked via the inhibitory G protein Gi. AD - Department of Physiology, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. FAU - Li, L AU - Li L FAU - Schafer, J A AU - Schafer JA LA - eng GR - DK-45768/DK/NIDDK PT - Journal Article PL - UNITED STATES TA - Am J Physiol JID - 0370511 RN - 0 (Dopamine Antagonists) RN - 0 (Enzyme Inhibitors) RN - 0 (Naphthalenes) RN - 0 (Phenanthridines) RN - 0 (Receptors, Dopamine D1) RN - 0 (Receptors, Dopamine D2) RN - 0 (dopamine D1A receptor) RN - 0 (receptors, dopamine D3) RN - 113-79-1 (Argipressin) RN - 121263-19-2 (calphostin C) RN - 137750-34-6 (receptors, dopamine D4) RN - 146-48-5 (Yohimbine) RN - 2062-78-4 (Pimozide) RN - 34316-15-9 (chelerythrine) RN - 51-43-4 (Epinephrine) RN - 51-61-6 (Dopamine) RN - 5786-21-0 (Clozapine) RN - 60-92-4 (Cyclic AMP) RN - 67227-56-9 (Fenoldopam) RN - 749-02-0 (Spiperone) RN - EC 2.7.1.37 (Protein Kinase C) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM MH - Animals MH - Argipressin/*pharmacology MH - Clozapine/pharmacology MH - Cyclic AMP/*metabolism MH - Dopamine/*pharmacology MH - Dopamine Antagonists/*pharmacology MH - Enzyme Inhibitors/pharmacology MH - Epinephrine/pharmacology MH - Fenoldopam/pharmacology MH - GTP-Binding Proteins/metabolism MH - In Vitro MH - Kidney Cortex/*metabolism MH - Kidney Tubules, Collecting/*metabolism MH - Kinetics MH - Male MH - Naphthalenes/pharmacology MH - Phenanthridines/pharmacology MH - Pimozide/pharmacology MH - Protein Kinase C/antagonists & inhibitors MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Dopamine D1/antagonists & inhibitors MH - Receptors, Dopamine D2/antagonists & inhibitors MH - Research Support, U.S. Gov't, P.H.S. MH - Spiperone/pharmacology MH - Time Factors MH - Yohimbine/pharmacology EDAT- 1998/08/05 MHDA- 1998/08/05 00:01 PST - ppublish SO - Am J Physiol 1998 Jul;275(1 Pt 2):F62-7. NR -------------------------------------------------------------------------------- 32: Noble EP et al. D2 and D4 dopamine receptor p...[PMID: 9603615] Related Articles, Books, LinkOut PMID- 9603615 OWN - NLM STAT- MEDLINE DA - 19980624 DCOM- 19980624 LR - 20041204 PUBM- Print IS - 0148-7299 VI - 81 IP - 3 DP - 1998 May 8 TI - D2 and D4 dopamine receptor polymorphisms and personality. PG - 257-67 AB - The relationship of various dimensions of temperament, measured by the Tridimensional Personality Questionnaire (TPQ), to polymorphisms of the D2 dopamine receptor (DRD2) and D4 dopamine receptor (DRD4) genes was determined in 119 healthy Caucasian boys who had not yet begun to consume alcohol and other drugs of abuse. Total Novelty Seeking score of the TPQ was significantly higher in boys having, in common, all three minor (A1, B1, and Intron 6 1) alleles of the DRD2 compared to boys without any of these alleles. Boys with the DRD4 7 repeat (7R) allele also had a significantly higher Novelty Seeking score than those without this allele. However, the greatest difference in Novelty Seeking score was found when boys having all three minor DRD2 alleles and the DRD4 7R allele were contrasted to those without any of these alleles. Neither the DRD2 nor the DRD4 polymorphisms differentiated total Harm Avoidance score. Whereas subjects having all three minor DRD2 alleles had a significantly higher Reward Dependence 2 (Persistence) score than subjects without any of these alleles, no significant difference in this personality score was found between subjects with and without the DRD4 7R allele. In conclusion, DRD2 and DRD4 polymorphisms individually associate with Novelty Seeking behavior. However, the combined DRD2 and DRD4 polymorphisms contribute more markedly to this behavior than when these two gene polymorphisms are individually considered. AD - Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles 90024-1759, USA. epnoble@ucla.edu FAU - Noble, E P AU - Noble EP FAU - Ozkaragoz, T Z AU - Ozkaragoz TZ FAU - Ritchie, T L AU - Ritchie TL FAU - Zhang, X AU - Zhang X FAU - Belin, T R AU - Belin TR FAU - Sparkes, R S AU - Sparkes RS LA - eng GR - AA-08020/AA/NIAAA PT - Journal Article PL - UNITED STATES TA - Am J Med Genet JID - 7708900 RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) SB - IM MH - Adolescent MH - Child MH - Exploratory Behavior MH - Gene Frequency MH - Genotype MH - Humans MH - Male MH - Personality/*genetics MH - *Polymorphism, Restriction Fragment Length MH - Questionnaires MH - Receptors, Dopamine D2/*genetics MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, P.H.S. MH - Reward EDAT- 1998/05/29 02:04 MHDA- 2000/06/20 09:00 AID - 10.1002/(SICI)1096-8628(19980508)81:3<257::AID-AJMG10>3.0.CO;2-E [pii] PST - ppublish SO - Am J Med Genet 1998 May 8;81(3):257-67. PR -------------------------------------------------------------------------------- 33: Long JC et al. Evidence for genetic linkage ...[PMID: 9603607] Related Articles, UniSTS, OMIM, Cited in PMC, Books, LinkOut PMID- 9603607 OWN - NLM STAT- MEDLINE DA - 19980624 DCOM- 19980624 LR - 20041117 PUBM- Print IS - 0148-7299 VI - 81 IP - 3 DP - 1998 May 8 TI - Evidence for genetic linkage to alcohol dependence on chromosomes 4 and 11 from an autosome-wide scan in an American Indian population. PG - 216-21 AB - To identify specific genes affecting vulnerability or resistance, we performed a whole-autosomal genome scan for genetic linkage to alcohol dependence in a Southwestern American Indian tribe. Genotypes at 517 autosomal microsatellite loci and clinical evaluations were available for 152 subjects belonging to extended pedigrees and forming 172 sib-pairs. Highly suggestive evidence for linkage emerged for two genomic regions using two- and multipoint sib-pair regression methods; both regions harbored neurogenetic candidate genes. The best evidence is seen with D11S1984 (nominal P = 0.00007, lod approximately equal to 3.1) on chromosome 11p, in close proximity to the DRD4 dopamine receptor and tyrosine hydroxylase (TH) genes. Good evidence is seen with D4S3242 (nominal P = 0.0002, lod approximately equal to 2.8) on chromosome 4p, near the beta1 GABA receptor gene. Interestingly, three loci in the alcohol dehydrogenase gene cluster on chromosome 4q showed evidence for linkage with two-point analyses, but not multipoint analysis. AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-8110, USA. jeff long@nih.gov FAU - Long, J C AU - Long JC FAU - Knowler, W C AU - Knowler WC FAU - Hanson, R L AU - Hanson RL FAU - Robin, R W AU - Robin RW FAU - Urbanek, M AU - Urbanek M FAU - Moore, E AU - Moore E FAU - Bennett, P H AU - Bennett PH FAU - Goldman, D AU - Goldman D LA - eng GR - 1 P41 RR03655/RR/NCRR PT - Journal Article PL - UNITED STATES TA - Am J Med Genet JID - 7708900 SB - IM MH - Adult MH - Alcoholism/ethnology/*genetics MH - Chromosomes, Human, Pair 11/*genetics MH - Chromosomes, Human, Pair 4/*genetics MH - Female MH - Genetic Predisposition to Disease MH - Genotype MH - Humans MH - Indians, North American/*genetics MH - *Linkage (Genetics) MH - Male MH - Matched-Pair Analysis MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, P.H.S. EDAT- 1998/05/29 02:04 MHDA- 2000/06/20 09:00 AID - 10.1002/(SICI)1096-8628(19980508)81:3<216::AID-AJMG2>3.0.CO;2-U [pii] PST - ppublish SO - Am J Med Genet 1998 May 8;81(3):216-21. PR -------------------------------------------------------------------------------- 34: Baron M. Mapping genes for personality...[PMID: 9577832] Related Articles, Books, LinkOut PMID- 9577832 OWN - NLM STAT- MEDLINE DA - 19980716 DCOM- 19980716 LR - 20041204 PUBM- Print IS - 1359-4184 VI - 3 IP - 2 DP - 1998 Mar TI - Mapping genes for personality: is the saga sagging? PG - 106-8 FAU - Baron, M AU - Baron M LA - eng GR - K05MH00176/MH/NIMH PT - News PL - ENGLAND TA - Mol Psychiatry JID - 9607835 RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) SB - IM MH - Alcoholism/epidemiology/genetics MH - Alleles MH - Confounding Factors (Epidemiology) MH - Disease Susceptibility MH - Ethnic Groups/genetics MH - Exploratory Behavior MH - False Positive Reactions MH - Female MH - Humans MH - Male MH - Minisatellite Repeats MH - Models, Psychological MH - Personality/*genetics MH - Personality Tests MH - Polymorphism, Genetic MH - Receptors, Dopamine D2/genetics/physiology MH - Reproducibility of Results MH - Research Design MH - Research Support, U.S. Gov't, P.H.S. MH - Substance-Related Disorders/epidemiology/genetics EDAT- 1998/05/13 MHDA- 1998/05/13 00:01 PST - ppublish SO - Mol Psychiatry 1998 Mar;3(2):106-8. NR -------------------------------------------------------------------------------- 35: Zenner MT et al. Expression and characterizati...[PMID: 9489994] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 9489994 OWN - NLM STAT- MEDLINE DA - 19980317 DCOM- 19980317 LR - 20041204 PUBM- Print IS - 0014-5793 VI - 422 IP - 2 DP - 1998 Jan 30 TI - Expression and characterization of a dopamine D4R variant associated with delusional disorder. PG - 146-50 AB - Multiple genetic polymorphisms of the human dopamine D4 receptor (hD4R) have been identified including a 12 bp repeat in exon 1 associated with a psychotic condition called delusional disorder. Competition binding assays revealed minor pharmacological differences between the recombinant A1 (normal) and A2 (delusional) proteins with respect to quinpirole and the antipsychotic clozapine, however no functional differences were detected for receptor activation by dopamine, epinephrine, or norepinephrine. Our results suggest that this polymorphism may only confer susceptibility to delusional disorder in combination with other genetic or environmental factors. AD - Hoffmann-La Roche, Pharmaceutical Research, Preclinical Neuroscience, Basel, Switzerland. FAU - Zenner, M T AU - Zenner MT FAU - Nobile, M AU - Nobile M FAU - Henningsen, R AU - Henningsen R FAU - Smeraldi, E AU - Smeraldi E FAU - Civelli, O AU - Civelli O FAU - Hartman, D S AU - Hartman DS FAU - Catalano, M AU - Catalano M LA - eng PT - Journal Article PL - NETHERLANDS TA - FEBS Lett JID - 0155157 RN - 0 (Antipsychotic Agents) RN - 0 (Dopamine Agonists) RN - 0 (Dopamine Antagonists) RN - 0 (Receptors, Dopamine D2) RN - 0 (Recombinant Proteins) RN - 137750-34-6 (receptors, dopamine D4) RN - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate)) RN - 51-41-2 (Norepinephrine) RN - 51-43-4 (Epinephrine) RN - 51-61-6 (Dopamine) RN - 5786-21-0 (Clozapine) RN - 85760-74-3 (Quinpirole) SB - IM MH - Animals MH - Antipsychotic Agents/pharmacology MH - CHO Cells MH - Clozapine/pharmacology MH - Dopamine/pharmacology MH - Dopamine Agonists/pharmacology MH - Dopamine Antagonists/pharmacology MH - Epinephrine/pharmacology MH - Guanosine 5'-O-(3-Thiotriphosphate)/metabolism MH - Hamsters MH - Humans MH - Kinetics MH - Norepinephrine/pharmacology MH - Polymorphism, Genetic MH - Quinpirole/pharmacology MH - Receptors, Dopamine D2/biosynthesis/drug effects/*genetics/physiology MH - Recombinant Proteins/metabolism MH - Schizophrenia, Paranoid/*genetics MH - Transfection MH - Variation (Genetics) EDAT- 1998/03/07 MHDA- 1998/03/07 00:01 AID - S0014579397016177 [pii] PST - ppublish SO - FEBS Lett 1998 Jan 30;422(2):146-50. NR -------------------------------------------------------------------------------- 36: Sullivan PF et al. No association between novelt...[PMID: 9433345] Related Articles, Books, LinkOut PMID- 9433345 OWN - NLM STAT- MEDLINE DA - 19980127 DCOM- 19980127 LR - 20041204 PUBM- Print IS - 0002-953X VI - 155 IP - 1 DP - 1998 Jan TI - No association between novelty seeking and the type 4 dopamine receptor gene (DRD4) in two New Zealand samples. PG - 98-101 AB - OBJECTIVE: In 1986 and 1987, Cloninger postulated the existence of the heritable behavioral trait of novelty seeking and its putative underpinnings in the dopaminergic systems of the ventral midbrain. Two widely reported studies found significant associations between novelty seeking and the type 4 dopamine receptor gene (DRD4), although a more recent study did not. The authors' objective was to investigate this association in two New Zealand samples. METHOD: The authors studied two nonoverlapping samples: subjects in a depression treatment trial (N = 86) and subjects from 14 pedigrees dense with alcoholism (N = 181). DRD4 genotyping was based on a standard protocol. RESULTS: Novelty seeking and DRD4 were not statistically associated. CONCLUSIONS: In these samples, there was no suggestion that the DRD4 polymorphism contributed to individual differences in the behavioral trait of novelty seeking. AD - Virginia Commonwealth University/Medical College of Virginia, Richmond, USA. sullivan@psycho.psi.vcu.edu FAU - Sullivan, P F AU - Sullivan PF FAU - Fifield, W J AU - Fifield WJ FAU - Kennedy, M A AU - Kennedy MA FAU - Mulder, R T AU - Mulder RT FAU - Sellman, J D AU - Sellman JD FAU - Joyce, P R AU - Joyce PR LA - eng PT - Journal Article PL - UNITED STATES TA - Am J Psychiatry JID - 0370512 RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) SB - AIM SB - IM MH - Adult MH - Alcoholism/diagnosis/genetics/psychology MH - Alleles MH - Depressive Disorder/diagnosis/genetics/psychology MH - Exploratory Behavior/*physiology MH - Female MH - Humans MH - Male MH - Mesencephalon/*physiology MH - New Zealand MH - Personality/genetics MH - Personality Inventory MH - Polymorphism, Genetic MH - Receptors, Dopamine D2/*genetics/physiology MH - Research Support, Non-U.S. Gov't EDAT- 1998/01/20 MHDA- 1998/01/20 00:01 PST - ppublish SO - Am J Psychiatry 1998 Jan;155(1):98-101. DR -------------------------------------------------------------------------------- 37: Eravci M et al. Dopamine receptor gene expres...[PMID: 9406938] Related Articles, Books, LinkOut PMID- 9406938 OWN - NLM STAT- MEDLINE DA - 19980219 DCOM- 19980219 LR - 20041117 PUBM- Print IS - 0169-328X VI - 50 IP - 1-2 DP - 1997 Oct 15 TI - Dopamine receptor gene expression in an animal model of 'behavioral dependence' on ethanol. PG - 221-9 AB - The steady-state levels of messenger RNA (mRNA) of five cloned dopamine (D) receptors were measured in five brain regions in rats in a recently developed animal model of 'behavioral dependence' on ethanol. One group of rats was given the choice between ethanol and water over a 9-month period and developed 'behavioral dependence' on ethanol (group a). This group was compared with a group given the choice between ethanol and water for only 2 months (not yet behaviorally dependent, group b), a group forced to consume ethanol as sole fluid over a 9-month period (not behaviorally dependent, group c) and ethanol-naive control rats. All groups were sacrificed 1 month after ethanol withdrawal. The concentrations of mRNA of D3-receptors in the limbic forebrain (which included the nucleus accumbens) were significantly lowered in groups a and b, but unchanged in group c. D3 mRNA levels were reduced in the hippocampus of group b and unchanged in the cortex, amygdala and striatum. No significant changes in the mRNA concentrations of D1-, D2-, D4- or D5-receptors were seen in the five brain regions in any group. In conclusion, chronic consumption of ethanol under the 'free-choice condition', which may best induce the drug-rewarding effect, leads to specific changes in the D3-receptor gene expression which were not seen after forced ethanol administration. Changes in D3 mRNA levels were, however, not a specific correlate of 'behavioral dependence', as they were also detected in rats not yet 'behaviorally dependent' (group b). AD - Department of Radiological Diagnostics and Nuclear Medicine, Klinikum Benjamin Franklin, Free University of Berlin, Germany. FAU - Eravci, M AU - Eravci M FAU - Grosspietsch, T AU - Grosspietsch T FAU - Pinna, G AU - Pinna G FAU - Schulz, O AU - Schulz O FAU - Kley, S AU - Kley S FAU - Bachmann, M AU - Bachmann M FAU - Wolffgramm, J AU - Wolffgramm J FAU - Gotz, E AU - Gotz E FAU - Heyne, A AU - Heyne A FAU - Meinhold, H AU - Meinhold H FAU - Baumgartner, A AU - Baumgartner A LA - eng PT - Journal Article PL - NETHERLANDS TA - Brain Res Mol Brain Res JID - 8908640 RN - 0 (Receptors, Dopamine) SB - IM MH - Alcohol Drinking MH - Alcoholism/*metabolism MH - Animals MH - Choice Behavior/*physiology MH - Disease Models, Animal MH - Gene Expression Regulation/*drug effects MH - Male MH - Rats MH - Rats, Wistar MH - Receptors, Dopamine/*genetics MH - Research Support, Non-U.S. Gov't EDAT- 1997/12/24 MHDA- 1997/12/24 00:01 PST - ppublish SO - Brain Res Mol Brain Res 1997 Oct 15;50(1-2):221-9. DR -------------------------------------------------------------------------------- 38: Van Tol HH. Structural and functional cha...[PMID: 9327945] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 9327945 OWN - NLM STAT- MEDLINE DA - 19971125 DCOM- 19971125 LR - 20041204 PUBM- Print IS - 1054-3589 VI - 42 DP - 1998 TI - Structural and functional characteristics of the dopamine D4 receptor. PG - 486-90 AD - Molecular Neurobiology Laboratory, Clarke Institute of Psychiatry, Toronto, Canada. FAU - Van Tol, H H AU - Van Tol HH LA - eng PT - Journal Article PL - UNITED STATES TA - Adv Pharmacol JID - 9015397 RN - 0 (Receptors, Dopamine D2) RN - 0 (Recombinant Proteins) RN - 137750-34-6 (receptors, dopamine D4) RN - 51-41-2 (Norepinephrine) RN - 51-43-4 (Epinephrine) RN - 51-61-6 (Dopamine) SB - IM MH - Alternative Splicing MH - Animals MH - Binding, Competitive MH - CHO Cells MH - Dopamine/pharmacology MH - Epinephrine/pharmacology MH - Exons MH - Hamsters MH - Humans MH - Mutagenesis, Site-Directed MH - Norepinephrine/pharmacology MH - Polymorphism, Genetic MH - Receptors, Dopamine D2/chemistry/genetics/*physiology MH - Recombinant Proteins/chemistry/metabolism MH - Transfection MH - Variation (Genetics) EDAT- 1997/11/05 MHDA- 1997/11/05 00:01 PST - ppublish SO - Adv Pharmacol 1998;42:486-90. NR -------------------------------------------------------------------------------- 39: Sander T et al. Dopamine D4 receptor exon III...[PMID: 9342196] Related Articles, Books, LinkOut PMID- 9342196 OWN - NLM STAT- MEDLINE DA - 19971120 DCOM- 19971120 LR - 20041204 PUBM- Print IS - 0148-7299 VI - 74 IP - 5 DP - 1997 Sep 19 TI - Dopamine D4 receptor exon III alleles and variation of novelty seeking in alcoholics. PG - 483-7 AB - A dysfunction of dopaminergic neurotansmission has been implicated in alcohol-seeking behavior. Recently, a significant association between the seven-repeat allele (DRD4*7R) of a 16 amino acid motif in the third exon of the dopamine D4 receptor gene (DRD4) and the personality trait of novelty seeking has been reported. Our population-based association study tested the hypothesis that the DRD4*7R variant predisposes to high levels of novelty seeking, which may underlie alcohol-seeking behavior. The genotypes of the expressed DRD4 exon III polymorphism were determined in 197 German controls and 252 German alcohol-dependent males, of whom 92 alcoholics completed the tridimensional personality questionnaire. We found no significant differences in the DRD4*7R frequencies between controls and alcoholics, including two subgroups (56 alcoholics with dissocial personality disorder according to ICD-10 and 89 alcoholics with severe withdrawal symptoms) with a high level of novelty seeking. The novelty-seeking scores did not differ significantly between alcoholics (including both subgroups) carrying long alleles with six or more repeats compared with those lacking long alleles. The present results do not provide evidence that the DRD4*7R allele contributes a common and relevant effect to alcohol-seeking behavior in our sample of alcoholics. AD - Department of Psychiatry, University Hospital Benjamin Franklin, Berlin, Germany. FAU - Sander, T AU - Sander T FAU - Harms, H AU - Harms H FAU - Dufeu, P AU - Dufeu P FAU - Kuhn, S AU - Kuhn S FAU - Rommelspacher, H AU - Rommelspacher H FAU - Schmidt, L G AU - Schmidt LG LA - eng PT - Journal Article PL - UNITED STATES TA - Am J Med Genet JID - 7708900 RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) SB - IM MH - Alcoholism/*genetics/*psychology MH - *Alleles MH - *Exons MH - *Exploratory Behavior MH - Humans MH - Male MH - Polymorphism, Genetic MH - Receptors, Dopamine D2/*genetics MH - Research Support, Non-U.S. Gov't MH - Risk EDAT- 1997/10/28 22:43 MHDA- 2000/06/20 09:00 AID - 10.1002/(SICI)1096-8628(19970919)74:5<483::AID-AJMG5>3.0.CO;2-P [pii] PST - ppublish SO - Am J Med Genet 1997 Sep 19;74(5):483-7. DR -------------------------------------------------------------------------------- 40: Rubinstein M et al. Mice lacking dopamine D4 rece...[PMID: 9323127] Related Articles, Compound via MeSH, Substance via MeSH, OMIM, Cited in PMC, Books, LinkOut PMID- 9323127 OWN - NLM STAT- MEDLINE DA - 19971020 DCOM- 19971020 LR - 20041204 PUBM- Print IS - 0092-8674 VI - 90 IP - 6 DP - 1997 Sep 19 TI - Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine. PG - 991-1001 AB - The human dopamine D4 receptor (D4R) has received considerable attention because of its high affinity for the atypical antipsychotic clozapine and the unusually polymorphic nature of its gene. To clarify the in vivo role of the D4R, we produced and analyzed mutant mice (D4R-/-) lacking this protein. Although less active in open field tests, D4R-/- mice outperformed wild-type mice on the rotarod and displayed locomotor supersensitivity to ethanol, cocaine, and methamphetamine. Biochemical analyses revealed that dopamine synthesis and its conversion to DOPAC were elevated in the dorsal striatum from D4R-/- mice. Based on these findings, we propose that the D4R modulates normal, coordinated and drug-stimulated motor behaviors as well as the activity of nigrostriatal dopamine neurons. AD - Instituto de Investigaciones en Ingenieria Genetica y Biologia Molecular, CONICET, and Depto. Quimica Biologica, FCEyN, Universidad de Buenos Aires, Argentina. FAU - Rubinstein, M AU - Rubinstein M FAU - Phillips, T J AU - Phillips TJ FAU - Bunzow, J R AU - Bunzow JR FAU - Falzone, T L AU - Falzone TL FAU - Dziewczapolski, G AU - Dziewczapolski G FAU - Zhang, G AU - Zhang G FAU - Fang, Y AU - Fang Y FAU - Larson, J L AU - Larson JL FAU - McDougall, J A AU - McDougall JA FAU - Chester, J A AU - Chester JA FAU - Saez, C AU - Saez C FAU - Pugsley, T A AU - Pugsley TA FAU - Gershanik, O AU - Gershanik O FAU - Low, M J AU - Low MJ FAU - Grandy, D K AU - Grandy DK LA - eng PT - Journal Article PL - UNITED STATES TA - Cell JID - 0413066 RN - 0 (Antipsychotic Agents) RN - 0 (Central Nervous System Depressants) RN - 0 (Dopamine Agents) RN - 0 (Levodopa) RN - 0 (Narcotics) RN - 0 (Receptors, Dopamine D2) RN - 102-32-9 (3,4-Dihydroxyphenylacetic Acid) RN - 137750-34-6 (receptors, dopamine D4) RN - 50-36-2 (Cocaine) RN - 51-61-6 (Dopamine) RN - 537-46-2 (Methamphetamine) RN - 5786-21-0 (Clozapine) RN - 64-17-5 (Ethanol) SB - IM MH - 3,4-Dihydroxyphenylacetic Acid/metabolism MH - Amino Acid Sequence MH - Animals MH - Antipsychotic Agents/pharmacology MH - Behavior, Animal/drug effects MH - Central Nervous System Depressants/*pharmacology MH - Clozapine/pharmacology MH - Cocaine/*pharmacology MH - Corpus Striatum/anatomy & histology/chemistry/metabolism MH - Dopamine/metabolism MH - Dopamine Agents/*pharmacology MH - Ethanol/*pharmacology MH - Genotype MH - Humans MH - Levodopa/analysis/pharmacokinetics MH - Locomotion/drug effects MH - Maternal Behavior/drug effects MH - Methamphetamine/*pharmacology MH - Mice MH - Mice, Knockout MH - Molecular Sequence Data MH - Motor Activity/drug effects MH - Mutagenesis, Site-Directed/physiology MH - Narcotics/*pharmacology MH - Nucleus Accumbens/chemistry/metabolism MH - Receptors, Dopamine D2/deficiency/*genetics MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, Non-P.H.S. MH - Research Support, U.S. Gov't, P.H.S. MH - Sensitivity and Specificity MH - Substantia Nigra/anatomy & histology/chemistry/metabolism MH - Transcription, Genetic/genetics EDAT- 1997/10/10 MHDA- 1997/10/10 00:01 PST - ppublish SO - Cell 1997 Sep 19;90(6):991-1001. DR -------------------------------------------------------------------------------- 41: Pascual J et al. [Neurochemistry of Parkinson'...[PMID: 9280680] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 9280680 OWN - NLM STAT- MEDLINE DA - 19970904 DCOM- 19970904 LR - 20041117 PUBM- Print IS - 0210-0010 VI - 25 Suppl 2 DP - 1997 Aug TI - [Neurochemistry of Parkinson's disease and parkinsonism plus] PG - S141-6 AB - The neurochemistry of Parkinson's disease and other degenerative parkinsonisms is reviewed, emphasizing the changes described in the dopaminergic system. Presynaptic dopaminergic markers are reduced over the striatum in all these degenerative parkinsonisms, dopamine receptor changes being more heterogeneous. While in Parkinson's disease D1 and D2 receptors remain preserved as compared to controls, in progressive supranuclear palsy there is a loss of nigral D1 receptors and of striatal D2 receptors. This finding has also been described in striatonigral degeneration. There are no clear data about the status of D3, D4 and D5 dopamine receptors in these conditions. The alterations in other neurotransmission systems, cholinegic, adrenergic, serotoninergic and peptidergic are, in general, less dramatic, although they have not been studied in detail. To conclude, further studies are necessary in these field, in these moment, however, the preservation of striatal D2 dopamine receptors is the neurochemical finding with the best correlation with the response to levodopa or other dopaminergic agonists. AD - Departamento de Medicina y Psiquiatria, Hospital Universitario Marques de Valdecilla, Santander, Espana. FAU - Pascual, J AU - Pascual J FAU - Misiego, M AU - Misiego M LA - spa PT - Journal Article PT - Review PT - Review, Tutorial TT - Neuroquimica de la enfermedad de Parkinson y parkinsonismos plus. PL - SPAIN TA - Rev Neurol JID - 7706841 RN - 0 (Receptors, Dopamine D1) RN - 0 (Receptors, Dopamine D2) RN - 51-41-2 (Norepinephrine) RN - 51-61-6 (Dopamine) RN - 51-84-3 (Acetylcholine) SB - IM MH - Acetylcholine/analysis MH - Autoradiography MH - Comparative Study MH - Dopamine/*analysis MH - English Abstract MH - Humans MH - Norepinephrine/analysis MH - Parkinson Disease/*etiology MH - Receptors, Dopamine D1/chemistry MH - Receptors, Dopamine D2/chemistry MH - Substantia Nigra/chemistry RF - 40 EDAT- 1997/08/01 MHDA- 1997/08/01 00:01 PST - ppublish SO - Rev Neurol 1997 Aug;25 Suppl 2:S141-6. NR -------------------------------------------------------------------------------- 42: Watts VJ et al. Activation of type II adenyla...[PMID: 9271339] Related Articles, Compound via MeSH, Substance via MeSH, Cited in PMC, Books, LinkOut PMID- 9271339 OWN - NLM STAT- MEDLINE DA - 19970905 DCOM- 19970905 LR - 20041204 PUBM- Print IS - 0026-895X VI - 52 IP - 2 DP - 1997 Aug TI - Activation of type II adenylate cyclase by D2 and D4 but not D3 dopamine receptors. PG - 181-6 AB - The D2-like dopamine receptors couple to a variety of signal transduction pathways, including inhibition of adenylate cyclase, mitogenesis, and activation of potassium channels. Although these effects are mediated via pertussis toxin-sensitive G proteins, G(i/o), it is likely that some of these effects are influenced by the release of G protein betagamma subunits. Type II adenylate cyclase (ACII) is highly regulated by multiple biochemical stimuli, including protein kinase C, forskolin, G protein alpha subunits, and G protein betagamma subunits. The ability of betagamma subunits to activate this enzyme in the presence of activated alpha(s) has been particularly well characterized. Although stimulation by betagamma subunits has been described as conditional on the presence of activated alpha(s), betagamma subunits also potentiate ACII activity after activation of protein kinase C. We created stable cell lines expressing ACII and the D2L receptor, the D3 receptor, or the D4.4 receptor. Activation of D2L or D4.4 receptors, but not D3 receptors, potentiated beta-adrenergic receptor/Gs-stimulated activity of ACII, as measured by the intracellular accumulation of cAMP. Similarly, stimulation of D2L or D4.4 receptors potentiated phorbol ester-stimulated ACII activity in the absence of activated alpha(s), whereas stimulation of D3 receptors did not. The effect of D2-like receptor stimulation was blocked by pretreatment with pertussis toxin and by inhibition of protein kinase C. We propose that activation of both D2L and D4.4 dopamine receptors potentiated phorbol-12-myristate-13-acetate-stimulated ACII activity through the release of betagamma subunits from pertussis toxin-sensitive G proteins. In contrast, the lack of D3 receptor-mediated effects suggests that stimulation of D3 receptors does not result in an appreciable release of betagamma subunits. AD - Veterans Affairs Medical Center and Department of Behavioral Neuroscience, Oregon Health Sciences University, Portland 97201, USA. wattsv@ohsu.edu FAU - Watts, V J AU - Watts VJ FAU - Neve, K A AU - Neve KA LA - eng GR - T32 DA07262/DA/NIDA PT - Journal Article PL - UNITED STATES TA - Mol Pharmacol JID - 0035623 RN - 0 (Receptors, Dopamine D2) RN - 0 (receptors, dopamine D3) RN - 137750-34-6 (receptors, dopamine D4) RN - 16561-29-8 (Tetradecanoylphorbol Acetate) RN - 51-61-6 (Dopamine) RN - 60-92-4 (Cyclic AMP) RN - 7683-59-2 (Isoproterenol) RN - 85760-74-3 (Quinpirole) RN - EC 2.7.1.37 (Protein Kinase C) RN - EC 4.6.1.1 (Adenylate Cyclase) SB - IM MH - Adenylate Cyclase/*metabolism MH - Cell Line MH - Cyclic AMP/metabolism MH - Dopamine/pharmacology MH - Drug Synergism MH - Enzyme Activation MH - Humans MH - Isoproterenol/pharmacology MH - Protein Kinase C/physiology MH - Quinpirole/pharmacology MH - Receptors, Dopamine D2/*physiology MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, Non-P.H.S. MH - Research Support, U.S. Gov't, P.H.S. MH - Tetradecanoylphorbol Acetate/pharmacology MH - Transfection EDAT- 1997/08/01 MHDA- 1997/08/01 00:01 PST - ppublish SO - Mol Pharmacol 1997 Aug;52(2):181-6. NR -------------------------------------------------------------------------------- 43: Dobashi I et al. Alcoholism and gene polymorph...[PMID: 9285967] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 9285967 OWN - NLM STAT- MEDLINE DA - 19971016 DCOM- 19971016 LR - 20050119 PUBM- Print IS - 0955-8829 VI - 7 IP - 2 DP - 1997 Summer TI - Alcoholism and gene polymorphisms related to central dopaminergic transmission in the Japanese population. PG - 87-91 AB - We examined the association between gene polymorphisms related to central dopaminergic transmission and alcoholism in the Japanese population. Polymorphic gene loci examined included those encoding the dopamine D2 receptor (NcoI site and Ser-Cys site), the dopamine D3 receptor (BalI site), the dopamine D4 receptor (48 bp tandem repeat) and the dopamine transporter (40 bp tandem repeat). The genotype distribution at the NcoI site in the dopamine D2 receptor gene differed significantly (p < 0.5) between alcoholic patients and control subjects. The frequency of 7 repeats at the 40 bp/DAT tended to be higher (p < 0.1), and that of 9 repeats tended to be lower (p < 0.1) in alcoholic patients than in control subjects. The possible effects of dopamine-related gene polymorphisms, which might predispose individuals to alcoholism, are discussed. AD - National Institute of Mental Health, National Center of Neurology and Psychiatry, Chiba, Japan. FAU - Dobashi, I AU - Dobashi I FAU - Inada, T AU - Inada T FAU - Hadano, K AU - Hadano K LA - eng PT - Journal Article PL - ENGLAND TA - Psychiatr Genet JID - 9106748 RN - 0 (Carrier Proteins) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Receptors, Dopamine D2) RN - 0 (dopamine transporter proteins) RN - 0 (receptors, dopamine D3) RN - 51-61-6 (Dopamine) RN - 52-90-4 (Cysteine) RN - 56-45-1 (Serine) SB - IM MH - Alcoholism/*genetics MH - Amino Acid Sequence MH - Carrier Proteins/*genetics MH - Cysteine MH - Dopamine/metabolism MH - Genotype MH - Humans MH - Japan MH - *Membrane Glycoproteins MH - *Membrane Transport Proteins MH - *Nerve Tissue Proteins MH - Polymerase Chain Reaction MH - *Polymorphism, Genetic MH - Receptors, Dopamine D2/*genetics MH - Reference Values MH - Repetitive Sequences, Nucleic Acid MH - Restriction Mapping MH - Serine EDAT- 1997/07/01 MHDA- 1997/07/01 00:01 PST - ppublish SO - Psychiatr Genet 1997 Summer;7(2):87-91. DR -------------------------------------------------------------------------------- 44: Okuyama S et al. In vitro and in vivo characte...[PMID: 9223539] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 9223539 OWN - NLM STAT- MEDLINE DA - 19970807 DCOM- 19970807 LR - 20041204 PUBM- Print IS - 0022-3565 VI - 282 IP - 1 DP - 1997 Jul TI - In vitro and in vivo characterization of the dopamine D4 receptor, serotonin 5-HT2A receptor and alpha-1 adrenoceptor antagonist (R)-(+)-2-amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl] pyrrolidin-3-yl]thiazole (NRA0045). PG - 56-63 AB - (R)-(+)-2-Amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl]+ ++pyrrolidin-3-yl]thiazole (NRA0045), a novel thiazole derivative, has high affinities for the human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 2.54, 0.55 and 0.54 nM, respectively. NRA0045 is approximately 91-fold more potent at the dopamine D4.2 receptor, compared with human cloned dopamine D2L receptor. NRA0045 also has high affinities for the serotonin (5-HT)2A receptor (Ki = 1.92 nM) and alpha-1 adrenoceptor (Ki = 1.40 nM) but weak affinities (IC50 values are approximately 1 microM) for six other neurotransmitter receptors (adenosine1, 5-HT1A, 5-HT1C, dopamine transporter, alpha2A and alpha2A) and negligible affinities (IC50 values are over 10(-5) M) for 42 other receptors, including neurotransmitters and hormones, ion channels and second messenger systems. Locomotor hyperactivity induced by methamphetamine (1 mg/kg i.p.) in mice was dose-dependently antagonized by NRA0045 (ED50 = 0.5 mg/kg i.p. and 1.9 mg/kg p.o., respectively). Methamphetamine (10 mg/kg i.p.)-induced stereotyped behavior in mice was dose-dependently antagonized by NRA0045, whereas NRA0045 did not exceed 50% inhibition even at the highest dose given (30 mg/kg i.p.). Catalepsy was dose-dependently and significantly induced by NRA0045 in rats, whereas NRA0045 did not exceed 50% induction even at the highest dose given (30 mg/kg i.p.). Thus NRA0045 blocks behaviors associated with activation of the mesolimbic/mesocortical dopaminergic neurons more selectively than behaviors associated with nigrostriatal dopaminergic neurons. In rats, tryptamine-induced clonic seizure, a 5-HT2 receptor-mediated behavior, was also dose-dependently inhibited by NRA0045 (ED50 = 1.7 mg/kg i.p.). Norepinephrine-induced lethality is regarded as being induced through the alpha-1 adrenoceptor. NRA0045 dose-dependently antagonized norepinephrine-induced lethality in rats (ED50 = 0.2 mg/kg i.p.). Thus NRA0045 may have a unique antipsychotic activity with regard to dopamine D4 and 5-HT2A receptors and alpha-1 adrenoceptor antagonistic activities, without producing the extrapyramidal side effects. AD - 1st Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., Ohmiya, Saitama, Japan. FAU - Okuyama, S AU - Okuyama S FAU - Chaki, S AU - Chaki S FAU - Yoshikawa, R AU - Yoshikawa R FAU - Suzuki, Y AU - Suzuki Y FAU - Ogawa, S AU - Ogawa S FAU - Imagawa, Y AU - Imagawa Y FAU - Kawashima, N AU - Kawashima N FAU - Ikeda, Y AU - Ikeda Y FAU - Kumagai, T AU - Kumagai T FAU - Nakazato, A AU - Nakazato A FAU - Nagamine, M AU - Nagamine M FAU - Tomisawa, K AU - Tomisawa K LA - eng PT - Journal Article PL - UNITED STATES TA - J Pharmacol Exp Ther JID - 0376362 RN - 0 (Adrenergic alpha-Antagonists) RN - 0 (Dopamine Antagonists) RN - 0 (NRA 0045) RN - 0 (Pyrrolidines) RN - 0 (Receptor, Serotonin, 5-HT2A) RN - 0 (Receptors, Adrenergic, alpha-1) RN - 0 (Receptors, Dopamine D2) RN - 0 (Receptors, Serotonin) RN - 0 (Serotonin Antagonists) RN - 0 (Thiazoles) RN - 137750-34-6 (receptors, dopamine D4) RN - 51-41-2 (Norepinephrine) SB - IM MH - Adrenergic alpha-Antagonists/metabolism/*pharmacology MH - Animals MH - COS Cells MH - Catalepsy/chemically induced MH - Dopamine Antagonists/metabolism/*pharmacology MH - Humans MH - Male MH - Mice MH - Mice, Inbred ICR MH - Motor Activity/drug effects MH - Norepinephrine/toxicity MH - Pyrrolidines/metabolism/*pharmacology MH - Rats MH - Rats, Wistar MH - Receptor, Serotonin, 5-HT2A MH - Receptors, Adrenergic, alpha-1/*antagonists & inhibitors MH - Receptors, Dopamine D2/*antagonists & inhibitors MH - Receptors, Serotonin/*drug effects MH - Serotonin Antagonists/metabolism/*pharmacology MH - Stereotyped Behavior/drug effects MH - Thiazoles/metabolism/*pharmacology EDAT- 1997/07/01 MHDA- 1997/07/01 00:01 PST - ppublish SO - J Pharmacol Exp Ther 1997 Jul;282(1):56-63. NR -------------------------------------------------------------------------------- 45: Kramer MS et al. The effects of a selective D4...[PMID: 9193198] Related Articles, Compound via MeSH, Substance via MeSH, Cited in PMC, Books, LinkOut PMID- 9193198 OWN - NLM STAT- MEDLINE DA - 19970627 DCOM- 19970627 LR - 20041204 PUBM- Print IS - 0003-990X VI - 54 IP - 6 DP - 1997 Jun TI - The effects of a selective D4 dopamine receptor antagonist (L-745,870) in acutely psychotic inpatients with schizophrenia. D4 Dopamine Antagonist Group. PG - 567-72 AB - BACKGROUND: Based mainly on the selective antagonism of clozapine at D4 compared with D2 dopamine receptors, hopes have run high that a selective D4 dopamine receptor antagonist might improve the pharmacological treatment of patients with schizophrenia. We report, to our knowledge, the first multicenter study of the antipsychotic potential of a highly specific D4 dopamine receptor antagonist (ie, L-745,870) in patients with acute schizophrenia. METHODS: Thirty-eight acutely psychotic and neuroleptic responsive (by history) newly admitted inpatients with schizophrenia were randomized to 4 weeks of double-blind treatment (2:1) with either L-745,870 (n = 26), 15 mg/d, or placebo (n = 12) after a 3- to 5-day placebo run-in period. RESULTS: Overall, a greater percentage of patients receiving L-745,870 compared with patients receiving placebo discontinued the study for insufficient therapeutic response (32% vs 16%). At the end of 4 weeks by last observation carried forward analysis, the mean change from baseline to week 4 on the total Brief Psychiatric Rating Scale favored placebo (i.e., -8 points [-15% change from baseline] vs -1 point [-2% change from baseline] for placebo vs L-745,870, P = .09). Similar differences in favor of placebo in changes from baseline mean scores were observed for the not carried forward analysis on the total Brief Psychiatric Rating Scale (P < .03), for not carried forward and last observation carried forward analyses on the sum of selected positive symptom items of the Brief Psychiatric Rating Scale, and for the Clinical Global Impression analysis (P = .03, last observation carried forward). A greater percentage of patients receiving L-745,870 had scores indicative of some level of worsening (compared with baseline) on the total Brief Psychiatric Rating Scale and the Clinical Global Impressions' Severity of Illness Scale as well as positive symptoms compared with those receiving placebo. CONCLUSION: The selective D4 dopamine receptor antagonist L-745,870 was ineffective as an antipsychotic for the treatment of neuroleptic responsive inpatients with acute schizophrenia. AD - Department of Clinical Neuroscience, Merch & Co Inc., West Point, Pa, USA. FAU - Kramer, M S AU - Kramer MS FAU - Last, B AU - Last B FAU - Getson, A AU - Getson A FAU - Reines, S A AU - Reines SA LA - eng PT - Clinical Trial PT - Journal Article PT - Randomized Controlled Trial PL - UNITED STATES TA - Arch Gen Psychiatry JID - 0372435 RN - 0 (Antipsychotic Agents) RN - 0 (Dopamine Antagonists) RN - 0 (Placebos) RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) RN - 302-17-0 (Chloral Hydrate) RN - 846-49-1 (Lorazepam) SB - AIM SB - IM EIN - Arch Gen Psychiatry 1997 Dec;54(12):1080 MH - Acute Disease MH - Adult MH - Antipsychotic Agents/pharmacology/*therapeutic use MH - Chloral Hydrate/therapeutic use MH - Dopamine Antagonists/*therapeutic use MH - Double-Blind Method MH - Drug Therapy, Combination MH - Female MH - *Hospitalization MH - Humans MH - Lorazepam/therapeutic use MH - Male MH - Placebos MH - Psychiatric Status Rating Scales MH - Receptors, Dopamine D2/drug effects MH - Schizophrenia/diagnosis/*drug therapy MH - Schizophrenic Psychology MH - Severity of Illness Index MH - Treatment Outcome EDAT- 1997/06/01 MHDA- 1997/06/01 00:01 PST - ppublish SO - Arch Gen Psychiatry 1997 Jun;54(6):567-72. NR -------------------------------------------------------------------------------- 46: Parsian A et al. No association between polymo...[PMID: 9184311] Related Articles, Books, LinkOut PMID- 9184311 OWN - NLM STAT- MEDLINE DA - 19970801 DCOM- 19970801 LR - 20041204 PUBM- Print IS - 0148-7299 VI - 74 IP - 3 DP - 1997 May 31 TI - No association between polymorphisms in the human dopamine D3 and D4 receptors genes and alcoholism. PG - 281-5 AB - The human dopamine D2 receptor gene (DRD2) has received considerable attention for the past several years as a potential candidate that may affect susceptibility to alcoholism. The association studies that compared the frequencies of alleles of DRD2 gene between alcoholics and control groups have produced equivocal results. Dopamine D3 and D4 receptor genes (DRD3 and DRD4) are in the same class as DRD2 but with different pharmacological properties. We have used relative risk and haplotype relative risk approaches to test associations between alleles of DRD3 and DRD4 genes and alcoholism. For relative risk studies 162 probands from multiple incidence alcoholic families have been compared to 89 psychiatrically normal controls. Haplotype relative risk approaches have used 29 alcoholic probands in which both parents were available for genotyping. The Bal I restriction enzyme site in DRD3 and tandem repeat (VNTR) in DRD4 genes polymorphisms were used to genotype the above samples. The results of relative risk approaches for both DRD3 and DRD4 genes were negative for comparisons of alcoholics and subtypes of alcoholics with normal controls. Haplotype relative risk approaches also were negative for both genes. These results suggest that any role played by these receptors may account for only part of the variation in susceptibility to alcoholism. AD - Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. FAU - Parsian, A AU - Parsian A FAU - Chakraverty, S AU - Chakraverty S FAU - Fisher, L AU - Fisher L FAU - Cloninger, C R AU - Cloninger CR LA - eng GR - AA09515/AA/NIAAA GR - MH31302/MH/NIMH PT - Journal Article PL - UNITED STATES TA - Am J Med Genet JID - 7708900 RN - 0 (Genetic Markers) RN - 0 (Receptors, Dopamine D2) RN - 0 (receptors, dopamine D3) RN - 137750-34-6 (receptors, dopamine D4) RN - EC 3.1.21- (endodeoxyribonuclease BalI) RN - EC 3.1.21.4 (Deoxyribonucleases, Type II Site-Specific) SB - IM MH - Alcoholism/*genetics/psychology MH - Alleles MH - Deoxyribonucleases, Type II Site-Specific/metabolism MH - Family MH - Female MH - Genetic Markers MH - Haplotypes/genetics MH - Humans MH - Male MH - Minisatellite Repeats/genetics MH - Monte Carlo Method MH - Polymorphism, Genetic/*genetics MH - Receptors, Dopamine D2/*genetics MH - Research Support, U.S. Gov't, P.H.S. MH - Risk Assessment EDAT- 1997/05/31 MHDA- 2000/06/20 09:00 AID - 10.1002/(SICI)1096-8628(19970531)74:3<281::AID-AJMG8>3.0.CO;2-T [pii] PST - ppublish SO - Am J Med Genet 1997 May 31;74(3):281-5. DR -------------------------------------------------------------------------------- 47: Kotler M et al. Excess dopamine D4 receptor (...[PMID: 9152990] Related Articles, Books, LinkOut PMID- 9152990 OWN - NLM STAT- MEDLINE DA - 19970730 DCOM- 19970730 LR - 20041204 PUBM- Print IS - 1359-4184 VI - 2 IP - 3 DP - 1997 May TI - Excess dopamine D4 receptor (D4DR) exon III seven repeat allele in opioid-dependent subjects. PG - 251-4 AB - Only in the past decade has a role of heredity in substance abuse been established as a result of extensive twin and family studies. More recently, several candidate genes have been investigated for their possible role in alcoholism and cocaine abuse. Specific genetic factors in opioid substance abuse have not been investigated in man, although animal studies suggest that quantitative trait loci (QTLs) can be identified that predispose mice both to morphine and alcohol preference. Central dopaminergic pathways figure prominently in drug-mediated reinforcement suggesting that dopamine receptors are likely candiadates for association with substance abuse in man. In addition, we recently reported an association between a human personality trait, Novelty Seeking and the long alleles (represented chiefly by the 7-repeat) of the D4 dopamine receptor (D4DR) exon III polymorphism. The personality trait of Novelty Seeking is also more pronounced in substance abusers, who score higher in this dimension than control subjects. The twin role of dopamine receptors in mediating Novelty Seeking and drugreinforcement prompted us to examine a group of Israeli heroin addicts for prevalence of the D4DR repeat polymorphism. We now show that the 7-repeat allele is significantly over-represented in the opioid-dependent cohort and confers a relative risk of 2.46. To our knowledge this is the first report of an association between a specific genetic polymorphism and opioid addiction. AD - Beersheva Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel. FAU - Kotler, M AU - Kotler M FAU - Cohen, H AU - Cohen H FAU - Segman, R AU - Segman R FAU - Gritsenko, I AU - Gritsenko I FAU - Nemanov, L AU - Nemanov L FAU - Lerer, B AU - Lerer B FAU - Kramer, I AU - Kramer I FAU - Zer-Zion, M AU - Zer-Zion M FAU - Kletz, I AU - Kletz I FAU - Ebstein, R P AU - Ebstein RP LA - eng PT - Journal Article PL - ENGLAND TA - Mol Psychiatry JID - 9607835 RN - 0 (Narcotics) RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) SB - IM MH - Adult MH - Alleles MH - Animals MH - Exons/*genetics MH - Humans MH - Male MH - Mice MH - Narcotics/*pharmacology MH - Receptors, Dopamine D2/*genetics MH - Research Support, Non-U.S. Gov't MH - Substance-Related Disorders/*genetics EDAT- 1997/05/01 MHDA- 1997/05/01 00:01 PST - ppublish SO - Mol Psychiatry 1997 May;2(3):251-4. PR -------------------------------------------------------------------------------- 48: Chang FM et al. The dopamine D4 receptor gene...[PMID: 9034534] Related Articles, Books, LinkOut PMID- 9034534 OWN - NLM STAT- MEDLINE DA - 19970430 DCOM- 19970430 LR - 20041117 PUBM- Print IS - 0006-3223 VI - 41 IP - 4 DP - 1997 Feb 15 TI - The dopamine D4 receptor gene (DRD4) is not associated with alcoholism in three Taiwanese populations: six polymorphisms tested separately and as haplotypes. PG - 394-405 AB - The dopaminergic system has been implicated in alcoholism but studies at the dopamine D2 receptor gene (DRD2), one of the five dopamine receptors, have not given a consistent picture of an association with alcoholism. We have now studied the dopamine D4 receptor gene (DRD4) using six polymorphisms, both separately and as haplotypes. Three groups of alcoholics from Taiwan (Atayal, Ami, and Han) diagnosed as having severe alcohol dependence using DSM-III-R criteria, together with nonalcoholics matched for gender, ethnic group, and geographic origin, were typed by polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymorphism (RFLP) for all six polymorphisms. Three out of six markers are polymorphic in all three Taiwanese populations. Although the prevalence rates of alcoholism are remarkably different, no highly significant association of this locus with alcoholism was observed in any of the three groups whether the analysis considered genotype distributions or allele frequencies at the three polymorphic markers considered individually and as haplotypes. Neither is there any obvious pattern in the data that covaries with or hints at a relationship with the very different prevalences of alcoholism in the groups studied. Especially because the powerful, multi-site haplotype analysis was not statistically significant in any of the population samples, we conclude that there is no association of the DRD4 locus with alcoholism in Taiwanese populations. AD - Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520-8005, USA. FAU - Chang, F M AU - Chang FM FAU - Ko, H C AU - Ko HC FAU - Lu, R B AU - Lu RB FAU - Pakstis, A J AU - Pakstis AJ FAU - Kidd, K K AU - Kidd KK LA - eng GR - AA09379/AA/NIAAA GR - MH30929/MH/NIMH GR - MH39239/MH/NIMH PT - Journal Article PL - UNITED STATES TA - Biol Psychiatry JID - 0213264 RN - 0 (Receptors, Dopamine) SB - IM MH - Alcoholism/*diagnosis/*genetics MH - Alleles MH - Comparative Study MH - Exons MH - Genotype MH - *Haplotypes MH - Humans MH - Molecular Biology MH - *Polymorphism, Genetic MH - Psychiatric Status Rating Scales MH - Receptors, Dopamine/*genetics MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, P.H.S. MH - Taiwan EDAT- 1997/02/15 MHDA- 1997/02/15 00:01 AID - S000632239600248X [pii] PST - ppublish SO - Biol Psychiatry 1997 Feb 15;41(4):394-405. DR -------------------------------------------------------------------------------- 49: Geijer T et al. Tyrosine hydroxylase and dopa...[PMID: 9046370] Related Articles, Books, LinkOut PMID- 9046370 OWN - NLM STAT- MEDLINE DA - 19970521 DCOM- 19970521 LR - 20041204 PUBM- Print IS - 0145-6008 VI - 21 IP - 1 DP - 1997 Feb TI - Tyrosine hydroxylase and dopamine D4 receptor allelic distribution in Scandinavian chronic alcoholics. PG - 35-9 AB - Associations of polymorphic genetic markers at the tyrosine hydroxylase (TH) and dopamine D4 receptor (DRD4) loci were examined in Scandinavian chronic alcoholics (n = 72) and control subjects (n = 67). Patients were divided into subgroups with regard to the presence of parental alcoholism and age of onset. Neither the TH nor the DRD4 allele distributions were significantly different when alcoholic samples were compared with control subjects. However, a tendency to high prevalence for 1 of the 5 TH alleles assayed (TH-K3) was observed in a subsample of 44 alcoholics characterized by late onset when compared with control subjects (27.3% vs. 10.6%, p = 0.041). Results suggest that no major influence on alcoholism is exerted through genes associated with the DRD4 or TH allelic markers examined. AD - Department of Clinical Neuroscience, Huddinge University Hospital, Stockholm, Sweden. FAU - Geijer, T AU - Geijer T FAU - Jonsson, E AU - Jonsson E FAU - Neiman, J AU - Neiman J FAU - Persson, M L AU - Persson ML FAU - Brene, S AU - Brene S FAU - Gyllander, A AU - Gyllander A FAU - Sedvall, G AU - Sedvall G FAU - Rydberg, U AU - Rydberg U FAU - Wasserman, D AU - Wasserman D FAU - Terenius, L AU - Terenius L LA - eng PT - Journal Article PL - UNITED STATES TA - Alcohol Clin Exp Res JID - 7707242 RN - 0 (Genetic Markers) RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) SB - IM MH - Adult MH - Aged MH - Alcoholism/classification/*genetics MH - *Alleles MH - Female MH - Genetic Markers/*genetics MH - Humans MH - Male MH - Middle Aged MH - Polymorphism, Genetic MH - Receptors, Dopamine D2/*genetics MH - Research Support, Non-U.S. Gov't MH - Sweden MH - Tyrosine 3-Monooxygenase/*genetics EDAT- 1997/02/01 MHDA- 1997/02/01 00:01 AID - 00000374-199702000-00005 [pii] PST - ppublish SO - Alcohol Clin Exp Res 1997 Feb;21(1):35-9. DR -------------------------------------------------------------------------------- 50: Lanau F et al. Epinephrine and norepinephrin...[PMID: 9003072] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 9003072 OWN - NLM STAT- MEDLINE DA - 19970221 DCOM- 19970221 LR - 20041204 PUBM- Print IS - 0022-3042 VI - 68 IP - 2 DP - 1997 Feb TI - Epinephrine and norepinephrine act as potent agonists at the recombinant human dopamine D4 receptor. PG - 804-12 AB - The catecholamines dopamine (DA), epinephrine (EP), and norepinephrine (NE) play important roles in learning and memory, emotional states, and control of voluntary movement, as well as cardiovascular and kidney function. They activate distinct but overlapping neuronal pathways through five distinct DA receptors (D1R-D5R) and at least 10 different adrenergic receptors (alpha 1a/b/c, alpha 2a/b/c-1/c-2, and beta 1/beta 2/beta 3). The D4R, which is localized to mesolimbic areas of the brain implicated in affective and emotional behavior, has a deduced amino acid sequence with homology to both adrenergic and dopaminergic receptor subtypes. We report here that DA, EP, and NE all show binding in the nanomolar range to three isoforms of the recombinant human D4R (hD4R): D4.2, D4.4, and D4.7. Submicromolar concentrations of DA, EP, and NE were sufficient to activate hD4R isoforms in two different functional assays: agonist-induced guanosine 5'-O-(3-[35S]thiotriphosphate) binding and modulation of adenylyl cyclase activity. DA was approximately fivefold more potent than EP and NE at the D4R, whereas activation of the human D2R required at least 100-fold higher catecholamine concentrations. Functional activation of the D4R by multiple neurotransmitters may provide a novel mechanism for integration of catecholamine signaling in the brain and periphery. AD - F. Hoffmann-La Roche AG, Basel, Switzerland. FAU - Lanau, F AU - Lanau F FAU - Zenner, M T AU - Zenner MT FAU - Civelli, O AU - Civelli O FAU - Hartman, D S AU - Hartman DS LA - eng PT - Journal Article PL - UNITED STATES TA - J Neurochem JID - 2985190R RN - 0 (Adrenergic alpha-Agonists) RN - 0 (Membrane Proteins) RN - 0 (Receptors, Dopamine D2) RN - 0 (Recombinant Proteins) RN - 10028-17-8 (Tritium) RN - 137750-34-6 (receptors, dopamine D4) RN - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate)) RN - 51-41-2 (Norepinephrine) RN - 51-43-4 (Epinephrine) RN - 51-61-6 (Dopamine) RN - 60-92-4 (Cyclic AMP) RN - 66428-89-5 (Forskolin) SB - IM MH - Adrenergic alpha-Agonists/metabolism/*pharmacology MH - Animals MH - Binding, Competitive/physiology MH - CHO Cells/chemistry/physiology MH - Cyclic AMP/metabolism MH - Dopamine/metabolism/pharmacology MH - Epinephrine/metabolism/*pharmacology MH - Forskolin/pharmacology MH - Guanosine 5'-O-(3-Thiotriphosphate)/metabolism/pharmacology MH - Hamsters MH - Humans MH - Membrane Proteins/metabolism MH - Norepinephrine/metabolism/*pharmacology MH - Receptors, Dopamine D2/*agonists/metabolism MH - Recombinant Proteins/drug effects/metabolism MH - Signal Transduction/drug effects MH - Tritium/diagnostic use EDAT- 1997/02/01 MHDA- 1997/02/01 00:01 PST - ppublish SO - J Neurochem 1997 Feb;68(2):804-12. NR -------------------------------------------------------------------------------- 51: Newman-Tancredi A et al. Noradrenaline and adrenaline ...[PMID: 9042615] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 9042615 OWN - NLM STAT- MEDLINE DA - 19970922 DCOM- 19970922 LR - 20041204 PUBM- Print IS - 0014-2999 VI - 319 IP - 2-3 DP - 1997 Jan 29 TI - Noradrenaline and adrenaline are high affinity agonists at dopamine D4 receptors. PG - 379-83 AB - The activity of monoamine neurotransmitters was examined at dopamine D4 receptors. In competition binding with [3H]spiperone, noradrenaline and adrenaline exhibited a high affinity binding component (KH = 12.1 nM and 5.0 nM, respectively), similar to that of dopamine (KH = 2.6 nM), whereas serotonin (5-hydroxytryptamine, 5-HT) and histamine had low affinity (Ki > 1000 nM). Noradrenaline and adrenaline acted as agonists at dopamine D4 receptors, stimulating receptor-mediated [35S]guanylyl-gamma-thiotriphosphate ([35S]GTP gamma S) binding (EC50 = 7.8 and 5.8 microM, respectively, versus 0.1 microM for dopamine). The dopamine D4 receptor-selective ligand, 3-(4-[4-chlorophenyl]piperazin-1-yl)methyl-1H-pyrrolo[2,3b]-pyridi ne (L 745,870) and the dopaminergic antagonists, spiperone, haloperidol and clozapine, inhibited noradrenaline-stimulated [35S]GTP gamma S binding whereas alpha 1-, alpha 2- and beta-adrenoceptor antagonists did not. These results indicate that dopamine D4 receptors are activated by noradrenaline and adrenaline, although at 50-100-fold higher concentrations than dopamine. AD - Department of Psychopharmacology, Institut de Recherches Servier, Croissy-sur-Seine, Paris, France. 101511,274@compuserve.com FAU - Newman-Tancredi, A AU - Newman-Tancredi A FAU - Audinot-Bouchez, V AU - Audinot-Bouchez V FAU - Gobert, A AU - Gobert A FAU - Millan, M J AU - Millan MJ LA - eng PT - Journal Article PL - NETHERLANDS TA - Eur J Pharmacol JID - 1254354 RN - 0 (3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine) RN - 0 (Dopamine Agonists) RN - 0 (Ligands) RN - 0 (Pyridines) RN - 0 (Pyrroles) RN - 0 (Receptors, Dopamine D2) RN - 0 (Sulfur Radioisotopes) RN - 137750-34-6 (receptors, dopamine D4) RN - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate)) RN - 51-41-2 (Norepinephrine) RN - 51-43-4 (Epinephrine) SB - IM MH - Animals MH - Binding, Competitive/drug effects MH - CHO Cells MH - Cell Membrane/drug effects/metabolism MH - Dopamine Agonists/*pharmacology MH - Epinephrine/*pharmacology MH - Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology MH - Hamsters MH - Humans MH - Ligands MH - Norepinephrine/*pharmacology MH - Pyridines/pharmacology MH - Pyrroles/pharmacology MH - Receptors, Dopamine D2/*agonists MH - Sulfur Radioisotopes/diagnostic use MH - Thermodynamics EDAT- 1997/01/29 MHDA- 1997/01/29 00:01 PST - ppublish SO - Eur J Pharmacol 1997 Jan 29;319(2-3):379-83. NR -------------------------------------------------------------------------------- 52: Jonsson E et al. Dopamine-related genes and th...[PMID: 8915563] Related Articles, Compound via MeSH, Substance via MeSH, Cited in PMC, Books, LinkOut PMID- 8915563 OWN - NLM STAT- MEDLINE DA - 19970513 DCOM- 19970513 LR - 20041117 PUBM- Print IS - 0006-3223 VI - 40 IP - 10 DP - 1996 Nov 15 TI - Dopamine-related genes and their relationships to monoamine metabolites in CSF. PG - 1032-43 AB - Monoamine metabolite (MM) levels in lumbar cerebrospinal fluid (CSF) are extensively used as indirect estimates of monoamine turnover in the brain. In this study we investigated genotypes for DNA polymorphisms in the D2 (DRD2), D3 (DRD3), and D4 (DRD4) dopamine receptor and tyrosine hydroxylase (TH) genes and their relationships to CSF MM in healthy volunteers (n = 66). Concentrations of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were corrected for back length, a confounding variable. Corrected MM levels were not related to age, gender, height, weight heredity, season or atmospheric pressure at sampling. Individuals with specific DRD2 and TH allele and genotype configurations significantly differed in HVA and MHPG concentrations. DRD3 homo- and heterozygotic genotypes had significantly different CSF 5-HIAA levels. DRD4 genotypes were not related to MM concentrations. The results suggest that specific DRD2, DRD3, and TH genotypes participate in the regulation of monoamine turnover in the central nervous system. Accordingly monoamine receptors and synthesizing enzyme genotypes appear to be variance factors influencing MM concentrations in CSF. The relationships found in this study support MM concentrations as markers for monoamine transmission in the human brain. AD - Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. FAU - Jonsson, E AU - Jonsson E FAU - Sedvall, G AU - Sedvall G FAU - Brene, S AU - Brene S FAU - Gustavsson, J P AU - Gustavsson JP FAU - Geijer, T AU - Geijer T FAU - Terenius, L AU - Terenius L FAU - Crocq, M A AU - Crocq MA FAU - Lannfelt, L AU - Lannfelt L FAU - Tylec, A AU - Tylec A FAU - Sokoloff, P AU - Sokoloff P FAU - Schwartz, J C AU - Schwartz JC FAU - Wiesel, F A AU - Wiesel FA LA - eng PT - Journal Article PL - UNITED STATES TA - Biol Psychiatry JID - 0213264 RN - 0 (Biogenic Monoamines) RN - 0 (Receptors, Dopamine) RN - 306-08-1 (Homovanillic Acid) RN - 51-61-6 (Dopamine) RN - 534-82-7 (Methoxyhydroxyphenylglycol) RN - 54-16-0 (Hydroxyindoleacetic Acid) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) SB - IM MH - Adult MH - Biogenic Monoamines/*cerebrospinal fluid/metabolism MH - Cerebrospinal Fluid/*metabolism MH - Dopamine/*genetics MH - Female MH - Genotype MH - Homovanillic Acid/cerebrospinal fluid MH - Humans MH - Hydroxyindoleacetic Acid/cerebrospinal fluid MH - Male MH - Mental Disorders/genetics MH - Methoxyhydroxyphenylglycol/cerebrospinal fluid MH - Middle Aged MH - Polymorphism, Genetic MH - Receptors, Dopamine/*genetics MH - Research Support, Non-U.S. Gov't MH - Seasons MH - Tyrosine 3-Monooxygenase/*genetics EDAT- 1996/11/15 MHDA- 1996/11/15 00:01 AID - 0006322395005811 [pii] PST - ppublish SO - Biol Psychiatry 1996 Nov 15;40(10):1032-43. NR -------------------------------------------------------------------------------- 53: Malhotra AK et al. The association between the d...[PMID: 9154232] Related Articles, Books, LinkOut PMID- 9154232 OWN - NLM STAT- MEDLINE DA - 19970609 DCOM- 19970609 LR - 20041204 PUBM- Print IS - 1359-4184 VI - 1 IP - 5 DP - 1996 Nov TI - The association between the dopamine D4 receptor (D4DR) 16 amino acid repeat polymorphism and novelty seeking. PG - 388-91 AB - Ebstein and colleagues have recently reported a significant association between the 7-repeat allele of the dopamine D4 receptor (D4DR) 16 amino acid repeat polymorphism and the personality trait of Novelty Seeking (NS) in 124 Israeli subjects. This study, and another study conducted in the US (although with a different personality measure) that observed a similar association, have generated wide interest in the identification of the genes involved in personality variation. We have determined D4DR genotypes in two groups of Finnish subjects; 193 psychiatrically screened normal controls and 138 alcoholic offenders and assessed NS with the Tridimensional Personality Questionnaire (TPQ). In normals, we find no significant association between NS and the 7-repeat allele despite similar allele frequencies and the use of the same personality measure as Ebstein et al. The group of alcoholic offenders have significantly higher NS than normals, however we fail to replicate the previous association in this group and, in fact, find a significant association in the opposite direction as previously observed. These data suggest that D4DR may require re-evaluation as a candidate gene for personality variation. AD - Experimental Therapeutics Branch, NIMH, Bethesda, MD 20892, USA. FAU - Malhotra, A K AU - Malhotra AK FAU - Virkkunen, M AU - Virkkunen M FAU - Rooney, W AU - Rooney W FAU - Eggert, M AU - Eggert M FAU - Linnoila, M AU - Linnoila M FAU - Goldman, D AU - Goldman D LA - eng PT - Journal Article PL - ENGLAND TA - Mol Psychiatry JID - 9607835 RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) SB - IM CIN - Mol Psychiatry. 2001 Nov;6(6):618-9. PMID: 11673788 MH - Adult MH - Alleles MH - Exploratory Behavior/*physiology MH - Finland MH - Genotype MH - Humans MH - Linkage (Genetics) MH - Male MH - Personality/genetics MH - Personality Tests MH - *Polymorphism, Genetic MH - Receptors, Dopamine D2/*genetics EDAT- 1996/11/01 MHDA- 1996/11/01 00:01 PST - ppublish SO - Mol Psychiatry 1996 Nov;1(5):388-91. DR -------------------------------------------------------------------------------- 54: Muramatsu T et al. Association between alcoholis...[PMID: 8929946] Related Articles, OMIM, Books, LinkOut PMID- 8929946 OWN - NLM STAT- MEDLINE DA - 19970512 DCOM- 19970512 LR - 20041204 PUBM- Print IS - 0022-2593 VI - 33 IP - 2 DP - 1996 Feb TI - Association between alcoholism and the dopamine D4 receptor gene. PG - 113-5 AB - A point mutation in the aldehyde dehydrogenase 2 gene (ALDH2(2) allele) is considered to be a genetic deterrent for alcoholism; however, 80 of 655 Japanese alcoholics had the mutant allele. Genotype factors that might increase susceptibility by overriding the deterrent showed a higher frequency of a five repeat allele of the dopamine D4 receptor 48 bp repeat polymorphism in alcoholics with ALDH2(2) than in 100 other alcoholics and 144 controls. Alcoholics with the five repeat allele also abused other drugs more often. These data suggest the involvement of the dopamine system in the development of alcoholism and other addictive behaviour. AD - National Institute on Alcoholism, Kurihama National Hospital, Japan. FAU - Muramatsu, T AU - Muramatsu T FAU - Higuchi, S AU - Higuchi S FAU - Murayama, M AU - Murayama M FAU - Matsushita, S AU - Matsushita S FAU - Hayashida, M AU - Hayashida M LA - eng PT - Journal Article PL - ENGLAND TA - J Med Genet JID - 2985087R RN - 0 (Isoenzymes) RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) RN - EC 1.2.1.3 (Aldehyde Dehydrogenase) SB - IM MH - Adult MH - Alcoholism/ethnology/*genetics MH - Aldehyde Dehydrogenase/deficiency/genetics MH - Alleles MH - Base Sequence MH - Female MH - Genes, Structural MH - Genetic Heterogeneity MH - Genetic Predisposition to Disease MH - Genotype MH - Humans MH - Isoenzymes/deficiency/genetics MH - Japan/epidemiology MH - Male MH - Middle Aged MH - Molecular Sequence Data MH - *Point Mutation MH - Receptors, Dopamine D2/deficiency/*genetics MH - Repetitive Sequences, Nucleic Acid MH - Substance-Related Disorders/genetics EDAT- 1996/02/01 MHDA- 1996/02/01 00:01 PST - ppublish SO - J Med Genet 1996 Feb;33(2):113-5. DR -------------------------------------------------------------------------------- 55: Adamson MD et al. DRD4 dopamine receptor genoty...[PMID: 7573171] Related Articles, Compound via MeSH, Substance via MeSH, Cited in PMC, Books, LinkOut PMID- 7573171 OWN - NLM STAT- MEDLINE DA - 19951107 DCOM- 19951107 LR - 20041204 PUBM- Print IS - 0148-7299 VI - 60 IP - 3 DP - 1995 Jun 19 TI - DRD4 dopamine receptor genotype and CSF monoamine metabolites in Finnish alcoholics and controls. PG - 199-205 AB - The DRD4 dopamine receptor is thus far unique among neurotransmitter receptors in having a highly polymorphic gene structure that has been reported to produce altered receptor functioning. These allelic variations are caused by a 48-bp segment in exon III of the coding region which may be repeated from 2-10 times. Varying the numbers of repeated segments changes the length, structure, and, possibly, the functional efficiency of the receptor, which makes this gene an intriguing candidate for variations in dopamine-related behaviors, such as alcoholism and drug abuse. Thus far, these DRD4 alleles have been investigated for association with schizophrenia, bipolar disorder, Parkinson's disease, and chronic alcoholism, and all have been largely negative for a direct association. We evaluated the DRD4 genotype in 226 Finish adult males, 113 of whom were alcoholics, many of the early onset type with features of impulsivity and antisocial traits. Genotype frequencies were compared to 113 Finnish controls who were free of alcohol abuse, substance abuse, and major mental illness. In 70 alcoholics and 20 controls, we measured CSF homovanillic acid (HVA), the major metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA). No association was found between a particular DRD4 dopamine receptor allele and alcoholism. CSF concentrations of the monoamine metabolites showed no significant difference among the DRD4 genotypes. This study of the DRD4 dopamine receptor in alcoholics is the first to be conducted in a clinically and ethnically homogeneous population and to relate the DRD4 genotype to CSF monoamine concentrations. The results indicate that there is no association of the DRD4 receptor with alcoholism. AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, DICBR, Rockville, MD 20852, USA. FAU - Adamson, M D AU - Adamson MD FAU - Kennedy, J AU - Kennedy J FAU - Petronis, A AU - Petronis A FAU - Dean, M AU - Dean M FAU - Virkkunen, M AU - Virkkunen M FAU - Linnoila, M AU - Linnoila M FAU - Goldman, D AU - Goldman D LA - eng PT - Journal Article PL - UNITED STATES TA - Am J Med Genet JID - 7708900 RN - 0 (Amines) RN - 0 (Receptors, Dopamine) RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) RN - 306-08-1 (Homovanillic Acid) SB - IM MH - Adult MH - Alcoholism/genetics/*metabolism MH - Alleles MH - Amines/*metabolism MH - Base Sequence MH - Finland MH - Homovanillic Acid/*cerebrospinal fluid MH - Humans MH - Male MH - Molecular Sequence Data MH - Polymerase Chain Reaction MH - Polymorphism, Genetic MH - Receptors, Dopamine/*genetics MH - *Receptors, Dopamine D2 EDAT- 1995/06/19 MHDA- 1995/06/19 00:01 PST - ppublish SO - Am J Med Genet 1995 Jun 19;60(3):199-205. DR -------------------------------------------------------------------------------- 56: Guo N et al. Receptor mechanisms mediating...[PMID: 7609873] Related Articles, Compound via MeSH, Substance via MeSH, Cited in PMC, Books, LinkOut PMID- 7609873 OWN - NLM STAT- MEDLINE DA - 19950817 DCOM- 19950817 LR - 20041117 PUBM- Print IS - 0306-4522 VI - 65 IP - 3 DP - 1995 Apr TI - Receptor mechanisms mediating clozapine-induced c-fos expression in the forebrain. PG - 747-56 AB - The atypical antipsychotic clozapine produces distinctly different regional patterns of c-fos expression in rat forebrain than does the prototypical neuroleptic haloperidol. While haloperidol-induced c-fos expression appears to be mediated by its D2 dopamine receptor antagonist properties, the mechanisms by which clozapine increases c-fos expression remain uncertain. Using a combination of brain lesion, pharmacological and immunohistochemical techniques, the present study sought to determine the receptor mechanisms by which clozapine increases the number of Fos-like immunoreactive neurons in various regions of the forebrain. To test whether serotonergic and/or noradrenergic systems are involved in clozapine-induced c-fos expression, rats received either 5,7-dihydroxytryptamine lesions of the medial forebrain bundle or 6-hydroxydopamine lesions of the dorsal noradrenergic bundle two weeks prior to clozapine (20 mg/kg) injections. Neither type of lesion affected clozapine-induced c-fos expression in the rat forebrain, suggesting that neither serotonergic nor noradrenergic mechanisms are involved in this action of clozapine. In another experiment, the 5-hydroxytryptamine2 receptor antagonist ritanserin (5 mg/kg), either alone or in combination with haloperidol (1 mg/kg), failed to mimic the pattern of c-fos expression produced by clozapine. This suggests that clozapine's antagonist actions at 5-hydroxytryptamine2 receptors cannot explain the unique pattern of regional c-fos expression produced by this compound. To determine whether the blockade of subtypes of the D2 dopamine receptor family may contribute to clozapine's effects, the dopamine receptor agonists quinpirole and 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) were injected 15 min prior to clozapine. Quinpirole produced a small but significant decrease in clozapine-induced c-fos expression in the medial prefrontal cortex, had larger effects in the lateral septum, and blocked clozapine's actions in the nucleus accumbens and major island of Calleja. Pretreatment with 7-OH-DPAT attenuated clozapine-induced c-fos expression in the nucleus accumbens and lateral septum, completely blocked the expression in the major island of Calleja, but was without effect in the medial prefrontal cortex. Given the different affinities of quinpirole and 7-OH-DPAT for D2, D3 and D4 receptors, these data suggest that clozapine-induced increases in c-fos expression in the nucleus accumbens, major island of Cajella and lateral septal nucleus are due to antagonist actions of this antipsychotic at D3 dopamine receptors. They also indicate that while antagonist actions at D4 receptors may contribute, the primary mechanisms by which clozapine increases c-fos expression in the medial prefrontal cortex remain to be determined. AD - Department of Psychiatry, University of British Columbia, Vancouver, Canada. FAU - Guo, N AU - Guo N FAU - Klitenick, M A AU - Klitenick MA FAU - Tham, C S AU - Tham CS FAU - Fibiger, H C AU - Fibiger HC LA - eng PT - Journal Article PL - ENGLAND TA - Neuroscience JID - 7605074 RN - 0 (Proto-Oncogene Proteins c-fos) RN - 0 (Receptors, Dopamine) RN - 50-67-9 (Serotonin) RN - 51-41-2 (Norepinephrine) RN - 51-61-6 (Dopamine) RN - 5786-21-0 (Clozapine) RN - 87051-43-2 (Ritanserin) SB - IM MH - Animals MH - Clozapine/*pharmacology MH - Dopamine/pharmacology MH - Immunohistochemistry MH - Male MH - Norepinephrine/pharmacology MH - Prosencephalon/*physiology MH - Proto-Oncogene Proteins c-fos/*genetics MH - Rats MH - Rats, Wistar MH - Receptors, Dopamine/*physiology MH - Research Support, Non-U.S. Gov't MH - Ritanserin/pharmacology MH - Serotonin/pharmacology EDAT- 1995/04/01 MHDA- 1995/04/01 00:01 AID - 030645229400552G [pii] PST - ppublish SO - Neuroscience 1995 Apr;65(3):747-56. NR -------------------------------------------------------------------------------- 57: Goldman D. Candidate genes in alcoholism...[PMID: 8612062] Related Articles, Books, LinkOut PMID- 8612062 OWN - NLM STAT- MEDLINE DA - 19960604 DCOM- 19960604 LR - 20041117 PUBM- Print IS - 1065-6766 VI - 3 IP - 3 DP - 1995 TI - Candidate genes in alcoholism. PG - 174-81 AB - Individual alleles identified by candidate gene analysis have been shown to profoundly influence certain complex behavioral syndromes including vulnerability to alcoholism. The alcohol and aldehyde dehydrogenase polymorphisms, ADH2(2) and ALDH2(2), respectively, are associated with lower vulnerability to alcoholism both in the Orient and also in North America among populations of Taiwanese and Koreans who have immigrated there. Protein structural variants have recently been identified for a series of genes involved in dopamine and serotonin function. Three dopamine receptors exhibit such structural variants, and these include the DRD2 dopamine receptor, which has three relatively rare amino acid substitutions. Structural polymorphisms were detected in five serotonin receptors (5HT1A, 5HT1Db, 5HT2A, 5HT2C, and 5HT7). Association studies between neurotransmitter gene variants and alcoholism are at an earlier stage than with ADH2(2)/ALDH2(2), but results are thus far negative (dopamine DRD4 receptor), equivocal (dopamine DRD2 receptor), or preliminary (tryptophan hydroxylase, 5HT2C and 5HT1Db). AD - Laboratory of Neurogenetics, NIAAA, NIH, Rockville, MD 20852, USA. FAU - Goldman, D AU - Goldman D LA - eng PT - Journal Article PT - Review PT - Review, Tutorial PL - UNITED STATES TA - Clin Neurosci JID - 9315128 SB - IM MH - Alcoholism/*genetics MH - Alleles MH - Genes/*genetics MH - Humans RF - 76 EDAT- 1995/01/01 MHDA- 1995/01/01 00:01 PST - ppublish SO - Clin Neurosci 1995;3(3):174-81. NR -------------------------------------------------------------------------------- 58: Tang L et al. Pharmacological and functiona...[PMID: 8301592] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 8301592 OWN - NLM STAT- MEDLINE DA - 19940310 DCOM- 19940310 LR - 20041117 PUBM- Print IS - 0022-3565 VI - 268 IP - 1 DP - 1994 Jan TI - Pharmacological and functional characterization of D2, D3 and D4 dopamine receptors in fibroblast and dopaminergic cell lines. PG - 495-502 AB - In order to study the properties of the D2-like dopamine receptors, D2, D3 and D4 clones were transfected into mouse Ltk- fibroblasts, CCL1.3, and a neuronal mesencephalic cell line, MN9D. Most of the derived antagonist and agonist inhibition constants were the same for a given receptor in either cell line as determined by saturation and competition binding experiments. The rank order potencies for antagonists are: eticlopride, D2 > D3 > D4; YM-09151-2, D2 = D4 > D3; spiperone, D2 = D3 > D4; (+)-butaclamol, D2 > D3 > D4; clozapine, D4 > D2 > D3; and for agonists, quinpirole, D3 = D4 > D2; 7-hydroxy-2-(di-n-propyl)-aminotetralin, D3 > D2 = D4. Functionally, D2 stimulation increases inositol phosphate levels in CCL1.3 cells but not in MN9D, whereas D2 activation inhibits forskolin-stimulated cyclic AMP levels in both cell lines. D4 stimulation has no effect on inositol phosphate metabolism in either cell type, but inhibits adenylate cyclase in MN9D cells. Both the D2 and D4 mediated decreases in cyclic AMP can be blocked by preincubation with pertussis toxin. D3 does not couple to these pathways in either cell line. Reverse transcription/polymerase chain reaction techniques were used to determine the availability of cellular signalling systems. Both CCL1.3 and MN9D cells have high levels of G alpha i2 expression, whereas neither cell expresses G alpha i1 or G alpha i3. These data imply that the D2 receptor couples to the G alpha i2 subtype in both cell lines, whereas D4 does not.(ABSTRACT TRUNCATED AT 250 WORDS) AD - Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri. FAU - Tang, L AU - Tang L FAU - Todd, R D AU - Todd RD FAU - Heller, A AU - Heller A FAU - O'Malley, K L AU - O'Malley KL LA - eng GR - MH28942/MH/NIMH GR - MH31302/MH/NIMH GR - MH45019/MH/NIMH GR - etc. PT - Journal Article PL - UNITED STATES TA - J Pharmacol Exp Ther JID - 0376362 RN - 0 (DNA Primers) RN - 0 (Inositol Phosphates) RN - 0 (Receptors, Dopamine) RN - 51-61-6 (Dopamine) RN - EC 3.6.1.- (GTP-Binding Proteins) RN - EC 4.6.1.1 (Adenylate Cyclase) SB - IM EIN - J Pharmacol Exp Ther 1994 Sep;270(3):1397 MH - Adenylate Cyclase/antagonists & inhibitors MH - Animals MH - Base Sequence MH - Cells, Cultured MH - DNA Primers MH - Dopamine/metabolism MH - Fibroblasts/*metabolism MH - GTP-Binding Proteins/metabolism MH - Inositol Phosphates/metabolism MH - Mice MH - Molecular Sequence Data MH - Neurons/*metabolism MH - Receptors, Dopamine/*drug effects/genetics/metabolism MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, P.H.S. MH - Transfection MH - Tumor Cells, Cultured EDAT- 1994/01/01 MHDA- 1994/01/01 00:01 PST - ppublish SO - J Pharmacol Exp Ther 1994 Jan;268(1):495-502. NR -------------------------------------------------------------------------------- 59: Zawilska JB. The role of dopamine in the r...[PMID: 7801792] Related Articles, Compound via MeSH, Substance via MeSH, Books, LinkOut PMID- 7801792 OWN - NLM STAT- MEDLINE DA - 19950125 DCOM- 19950125 LR - 20041204 PUBM- Print IS - 0065-1400 VI - 54 Suppl DP - 1994 TI - The role of dopamine in the regulation of melatonin biosynthesis in vertebrate retina. PG - 47-56 AB - The vertebrate retina rhythmically synthesizes melatonin, a hormone involved in the regulation of several intraocular processes cued by environmental lighting conditions. The rhythm of retinal melatonin production, with maximal synthesis at night in darkness, is driven by the photoperiodic environment to which animals are exposed, and is generated by an endogenous circadian clock(s). This article reviews data on the role of dopamine, an established retinal neurotransmitter and paracrine factor, as a mediator of acute suppressive and entrainment action of light on the melatonin generating system in the retina. Special emphasis is given to the characterization of dopamine receptor types involved in the control of retinal melatonin formation. AD - Department of Pharmacodynamics, Medical University of Lodz, Poland. FAU - Zawilska, J B AU - Zawilska JB LA - eng PT - Journal Article PT - Review PT - Review, Tutorial PL - POLAND TA - Acta Neurobiol Exp (Wars) JID - 1246675 RN - 0 (Receptors, Dopamine) RN - 0 (Receptors, Dopamine D2) RN - 137750-34-6 (receptors, dopamine D4) RN - 51-41-2 (Norepinephrine) RN - 51-61-6 (Dopamine) RN - 73-31-4 (Melatonin) SB - IM MH - Animals MH - *Circadian Rhythm MH - Dopamine/*physiology MH - Homeostasis MH - Humans MH - Melatonin/*biosynthesis MH - Norepinephrine/physiology MH - Pineal Gland/*metabolism MH - Receptors, Dopamine/physiology MH - *Receptors, Dopamine D2 MH - Research Support, Non-U.S. Gov't MH - Retina/*metabolism MH - Vertebrates RF - 70 EDAT- 1994/01/01 MHDA- 1994/01/01 00:01 PST - ppublish SO - Acta Neurobiol Exp (Wars) 1994;54 Suppl:47-56. NR --------------------------------------------------------------------------------