Biologie du Comportement, Université Catholique de Louvain, 1 Place Croix du Sud, 1348 Louvain-la-Neuve, Belgium
* Author to whom correspondence should be addressed at: Biologie du Comportement, Université Catholique de Louvain, 1 Place Croix du Sud, 1348 Louvain-la-Neuve, Belgium. Tel.: +32 10 474384; Fax: +32 10 474094; E-mail: dewitte{at}bani.ucl.ac.be
(Received 6 August 2004; first review notified 1 September 2004; in revised form 17 September 2004; accepted 1 October 2004)
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ABSTRACT |
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INTRODUCTION |
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Chronic ethanol administration has a dual effect on the cannabinoid receptor, increasing the level of both endogenous cannabinoid agonists, anandamide and 2-arachidonylglycerol, while downregulating the CB1 receptor number and function, thereby suggesting a role for the endocannabinoid system in the neurobiological effects of ethanol (Basavarajappa et al., 1998b, 2000; Basavarajappa and Hungund, 1999a
,b
). Nonetheless, ethanol did not produce any effects on CB1 receptor binding and mRNA levels in rats (Gonzalez et al., 2002
). However, a recent study by Ortiz et al. (2004)
showed that forced consumption of high quantity of ethanol for a long period significantly decreased the gene expression of the CB1 receptors in the caudate-putamen, the ventromedial nucleus of hypothalamus and both CA1 and CA2 fields of the hippocampus. The last finding is in accordance with Basavarajappa et al. (1998)
and Basavarajappa and Hungund (1999a)
. The result obtained by Gonzalez et al. (2002)
could be due to differences in the quantity of ethanol and the duration of ethanol administration.
CP-55,940, a CB1 receptor agonist, promoted alcohol craving in rats (Gallate et al., 1999), as well as voluntary ethanol intake in Sardinian alcohol-preferring (sP) rats (Colombo et al., 2002
). WIN-55,2122, another CB1 receptor agonist, also promoted voluntary ethanol intake in sP rats (Colombo et al., 2002
).
Numerous studies have shown that the CB1 receptor antagonist SR 141716 reduces ethanol intake (Arnone et al., 1997; Colombo et al., 1998
; Rodríguez de Fonseca et al., 1999
; Freedland et al., 2001
) and ethanol craving (Gallate and McGregor, 1999
) in different rat strains. In addition, SR 141716 suppressed the ethanol deprivation effects (i.e. the temporary increase in ethanol intake after a period of ethanol withdrawal) in sP rats (Serra et al., 2002
). All these results suggest that the blocking of CB1 receptor decreases the consumption of ethanol. Nonetheless, it is also important to mention that in our previous study in Wistar rats, we showed that the cannabinoid receptor antagonist SR 141716 profoundly altered ethanol preference in chronically pulmonary alcoholised rats depending on the dose and time of administration. Doses of 3 or 10 mg/kg/day, administered during chronic pulmonary alcoholization enhanced ethanol preference whereas its administration during the ethanol withdrawal stage after alcoholization induced a decrease in ethanol preference (Lallemand and De Witte, 2001
). We have also shown that the action of SR 141716 was dependent on a number of factors, including the duration of ethanol intoxication as well as the number of ethanol re-exposures and ethanol withdrawals (Lallemand et al., 2004
).
All these previous studies used antagonists and agonists of CB1 receptors. In certain circumstances, some antagonists have side-effects, which could alter/modify their actions. For example, SR-141716, a CB1 receptor antagonist, can show agonist property (Shire et al., 1999).
An alternative to avoid these possible pharmacological side-effects is the use of null mutant mice. The development of transgenic CB1 knockout mice has provided the opportunity to study the role of the CB1 receptor system in the regulation of ethanol consumption (Ledent et al., 1999; Zimmer et al., 1999
).
mice with CD1 background showed decreased ethanol intake and preference. These effects were associated with a dramatic sensitivity to the hypothermic and hypolocomotor effects in response to low doses of ethanol (Naassila et al., 2004
). These mice also showed an increased intensity of ethanol withdrawal-induced convulsions. Female
mice consumed more ethanol than male
mice; in addition, this gender difference was observed in both genotypes female
mice showed a decreased ethanol consumption compared with that of female
mice, but did consume the same quantity of ethanol as did male
mice. Hungund et al. (2003)
observed similar results, although the gender difference in ethanol consumption observed between female and male
mice was abolished in
mice. These results were also observed in the study of Poncelet et al. (2003)
using
mice with C57BL/6 x 129/Ola F2 background.
with C57BL/6J background had a higher preference for ethanol but only for a few days (Racz et al., 2003
). After the cessation of chronic ethanol administration, these mice did not exhibit withdrawal symptoms. After mild intermittent foot-shock stress, alcoholized
mice did not consume an increased amount of ethanol as did the
mice for the next 24 h. The activation of CB1 receptors in wild-type mice will also contribute to the high ethanol preference exhibited by C57BL/6J mice (Wang et al., 2003
) as SR 141716 is able to reduce ethanol drinking when administered to these mice and not in
mice. Young and old
mice with this genetic background displayed low ethanol preference. On the contrary,
mice presented an age-dependent decline in ethanol preference, suggesting that the decline in ethanol preference is related to a loss of cannabinoid signalling in the limbic forebrain.
It could be hypothesized that there was an interaction of gender and expression of phenotype associated with the CB1 gene mutation. The total fluid intake was similar between the different genotypes, although differences were evident between males and females within the same genotype. male mice did not show the acute ethanol-induced increase in dopamine levels in nucleus accumbens compared with
mice, which would indicate that activation of the limbic system was required for the reinforcing effects of ethanol (Hungund et al., 2003
).
The purpose of our study was to investigate the effect of a low to high acute intraperitoneal ethanol injection on blood ethanol concentration (BEC), as well as the effects of non-forced ethanol administration and forced chronic pulmonary ethanol intoxication on ethanol preference by comparing and
mice to ascertain the precise involvement of the cannabinoid system on ethanol-related behavioural effects.
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MATERIALS AND METHODS |
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Acute ethanol experiments
BEC was assayed in and
, 3032 g, 12-weeks-old, male mice, housed 5/cage, after an intraperitoneal injection of ethanol. The experiment was carried out in their home cages. Blood samples were collected from the retro-orbital sinus under slight ether anaesthesia where necessary, into haematocrit tubes at 20, 40 min and 1, 2, 4, 9 and 12 h, after either 1 or 3 g/kg ethanol doses (15% v/v), while an additional two samples at 14 and 16 h were also collected after the 5 g/kg dose. This procedure followed the schedule of blood drawing used by Bruguerolle and Dubus (1993)
, Bruguerolle et al. (1994)
and Hettiarachchi et al. (2001)
. Blood from each haematocrit tube was transferred into microcentrifuge tubes containing sodium fluoride as an anticoagulant. The concentration of blood ethanol was assayed by an alcohol-dehydrogenase-based method (Aufrère et al., 1997
).
Chronic ethanol experiments
Non-forced ethanol administration experiments. and
, 3032 g, 12-weeks-old, male mice, were housed 2/cage. Fluid intake (water and 10% v/v ethanol when present) was recorded every 1 or 2 days, and body weight every week.
Free-choice period. Two drinking bottles were placed in each cage, one containing tap water and the other, 10% v/v ethanol solution. The mice had continuous access to the drinking tips of both tubes. The position of the tubes was changed every day, in order to avoid possible bias due to place preference. The ratio of the 24 h intake from the ethanol bottle versus total fluid intake was used to define preference and the absolute amount (g/kg body weight/day) of ethanol consumed was also calculated.
Forced chronic pulmonary ethanol administration procedure. The motility of and
, 3032 g, 12 weeks old, male mice, was recorded, after 3 weeks of acclimatization, for 18 h by the MacLab system, the recordings being combined for each hourly interval. The apparatus has been described in detail previously (Lallemand and De Witte, 2001
).
Forced chronic alcoholization was induced in these mice, housed in pairs of two, within a plastic chamber (120 x 60 x 60 cm) by pulmonary inhalation of a mixture of ethanol and air. The mixture was pulsed into the chamber via a mixing system that allowed the quantity of ethanol to be increased every day, so that the average BEC continued to rise (Le Bourhis, 1975; Aufrère et al., 1997
) during the experimental procedure. The animals remained for 12 days in the alcohol chamber. The chamber temperature ranged between 2830°C (Terdal and Crabbe, 1994
; Finn and Crabbe, 1999
). BECs were determined regularly during the chronic alcoholization. Blood from each haematocrit tube was transferred into microcentrifuge tubes containing sodium fluoride as an anticoagulant. The concentration of blood ethanol was assayed by an alcohol-dehydrogenase-based method.
Withdrawal motility and free-choice period. At the end of the forced chronic pulmonary alcoholisation period the motility and ethanol preference was studied in these two groups of mice. For the measurement of ethanol preference, the mice from each strain underwent three successive steps (Le Bourhis, 1977) on cessation of the chronic ethanol intoxication. First, full beverage deprivations, i.e. the drinking bottles were removed during the last 6 h of the chronic alcoholization procedure and the following 18 h of the withdrawal period. The motility of each mouse was recorded during these 18 h using the same apparatus described above. Secondly, a 10% (v/v) ethanol solution was given as the sole drinking fluid during the following 24 h. Thirdly, a free-choice beverage situation [water vs 10% (v/v) ethanol solution] was presented for a period of 39 days. During this free-choice period, the fluid consumptions were recorded daily and ethanol consumption expressed as a percentage of total fluid intakes and as ethanol intake in g/kg of body weight. The positions of the drinking bottles were changed every day to avoid position preference. BECs were assayed at different time points during the free-choice period by the method described above. The weight of animals was recorded every 3 or 4 days.
In all experiments, the results are presented as mean ± standard error (SE) except where stated otherwise. In all experiments, groups were compared by two-way analysis of variance (ANOVA) (genotype; time) with repeated measures on time. Where appropriate, post hoc pair wise comparisons were analysed by the least-significant difference test of multiple comparisons (Fisher LSD protected t-test) (GB-STAT 5.3 for Windows, Dynamic Microsystems, Silver Spring, MD, USA). Criterion for significance was set at P < 0.05 for all tests.
The Belgian Governmental Agency under the authorized number LA 1220028 as well as the European Communities Council Directive concerning the Use of Laboratory Animals approved these experiments.
Products
Absolute ethanol, used in the free-choice paradigm and acute experiment, was obtained from Labotec (La Gleize, Belgium). Ethanol at 15% (w/v) was prepared for i.p. injection in 0.9% saline. Ethanol at 97% was obtained from Belgalco SA (Belgium). Sodium fluoride was from Sigma Aldrich, (Steinheim, Germany).
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RESULTS |
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At the conclusion of the study, the mice showed a significantly lower mean weight in comparison to controls [F(1,38) = 7.3466, P = 0.01]. The mean weights were 32.18 ± 0.62 and 30.16 ± 0.36 g, respectively, for
and
mice.
Free choice. mice showed a significantly reduced ethanol preference (expressed as a percentage of total fluid intake) in comparison to control mice [F(1,12) = 8.6787; P = 0.0122] (Fig. 2A). There was also a significant interaction between genotype and time [F(8,96) = 2.1965, P = 0.0342]. Nonetheless, when ethanol preference is expressed as ethanol intake in g/kg of body weight, the genotype significance disappeared totally and only the interaction remained [F(38,418) = 3.9539; P < 0.0001] (Fig. 2B). The mean ethanol intake over the time of the experiment was 12.28 ± 0.48 and 13.12 ± 0.59 g/kg/day, respectively, for
and
mice.
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During the free-choice period the total consumption (water + 10% v/v ethanol) of mice was not significantly different in comparison to control mice [F(1,26) = 3.3544, P = 0.0785] (data not shown), but there was a significant interaction between genotype and time [F(8,208) = 4.3224, P < 0.0001]. Nonetheless, the total consumption of
mice was always above that of control mice. The mean consumptions over the time of the experiment were 9.67 ± 0.70 and 7.23 ± 0.33 ml/24 h, respectively, for
and
male mice.
Forced chronic ethanol pulmonary administration experiments. The motility of mice, prior to forced chronic ethanol pulmonary administration, was not significantly different in comparison to
mice [F(1,510) = 0.7872, P = 0.382].
In the mice the mean BEC assayed at different time points during the forced chronic alcoholization regime were significantly different than the mean levels in the
mice [F(1,26) = 25.887, P < 0.0001] characterized by a significant higher BEC level at both 10 and 11 days after the commencement of forced chronic pulmonary alcoholization. [F(6,156) = 7.931, P < 0.0001] (Fig. 3). At 10 days, the mean BEC was 3 fold higher in the
mice than in the
mice, whereas at 11 days, it showed a 2 fold increase. However, on Day 13 no significant difference in mean BEC was assayed.
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mice had a significantly lower body weight than
mice [F(1,38) = 7.3466, P = 0.01]. The mean weights over the time of the experiment were 30 ± 0.46 and 32 ± 0.62 g, respectively, for
and
mice.
Following forced chronic pulmonary alcoholization, similar motilities were assayed for both and control mice [F(1,340) = 0.8442, P = 0.3704] as they were also similar prior to the chronic pulmonary alcoholization.
Free choice. During the first 24 h period after forced chronic pulmonary alcoholisation, there were no significant differences in ethanol consumption between and
mice [F(1,11) = 0.4936, P = 0.4969]. The mean ethanol consumptions in the alcoholized
group and in the alcoholized
group were, 18.69 ± 1.69 ml and 16.75 ± 1.29 ml, respectively. During the free-choice period, ethanol preference, expressed as percentage of total fluid consumption, of
mice showed no significance at the genotype level when compared with
mice [F(1,11) = 2.1819, P = 0.1677] (Fig. 4A). There was also absence of significance when ethanol preference was expressed as ethanol intake/kg body weight [F(1,11) = 1.6614, P = 0.2239] (Fig. 4B). Nonetheless, in both representations of ethanol preference, there were always significant interactions between genotype and time [F(38,418) = 2.345, P < 0.0001 and F(38,418) = 3.9539, P < 0.0001, respectively, for percentage of total fluid consumption (Fig. 4A) and ethanol intake expressed in g/kg body weight (Fig. 4B)]. The mean ethanol intakes in all experiments were 17.96 ± 0.52 and 22.05 ± 0.69 g/kg, respectively, for
and
mice.
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The total liquid consumption was not significantly different in and
mice [F(1,11) = 1.3981, P = 0.262], although there was a significant interaction between genotype and time [F(38,418) = 3.5209, P < 0.0001]. The total consumption values for
mice were always greater or at the same level for those of the
mice.
During the free-choice paradigm, there was no significant difference between the BEC values at the genotype level [F(1,4) = 3.092, P = 0.1535]; the values assayed being less than 0.02 g/l in both groups of mice (data not shown). However, there was a significant interaction between genotype and time [F(5,20) = 2.849, P = 0.0422], as well as for time [F(5,20) = 20.192, P < 0.0001].
During the free-choice period, mice showed a significantly lower body weight than the
mice [F(1,18) = 9.5004, P = 0.0064] (data not shown). There was also a significant interaction between genotype and time [F(10,180) = 6.851, P < 0.0001]. The body weight of
mice at the beginning of the study was 31.2 ± 0.6 and 31.14 ± 0.67 g at its conclusion. The body weight of
mice was 32.36 ± 0.75 g at the beginning of the study and was 37.64 ± 1.39 g at the end.
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DISCUSSION |
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In mice with non-forced ethanol administration, ethanol preference ratio was significantly reduced in mice, but when ethanol preference was expressed as g/kg body weight per day, no significances appeared. These results are in agreement with those obtained by Wang et al. (2003)
for ethanol preference ratio. Nonetheless, other studies by Hungund et al. (2003)
and Poncelet et al. (2003)
observed that ethanol intake expressed in g/kg body weight/day was significantly reduced in
mice as well. This discrepancy on the preference in ethanol intake was unclear. In our study, the absence of significance in preference as expressed in g/kg body weight/day is mainly the result of a higher, but not significant, total liquid intake of the
mice.
In chronically forced alcoholized mice, the BEC in mice peaked faster than in
mice, although the maximum values obtained were not significantly different. This result has not been observed in previous studies, although Colombo et al. (1998b) showed that the antagonism at CB1 cannabinoid receptors did not modify ethanol metabolism. In our study, the difference between
and
mice was noted only during the increase of BEC but not at the end of the chronic alcoholization period. Unlike other chronic alcoholization procedures, our protocol of chronic alcoholization is a forced one, i.e. animals were unable to adjust the amount of ethanol ingested by themselves. Our procedure of chronic alcoholization induced other mechanisms involved in ethanol metabolism microsomal ethanol oxidizing system MeOS/cytochrome P450IIE (Lieber, 1999
) and alcohol dehydrogenase (Kishimoto et al., 1995
), which have not been studied to date in these knockout animals.
After forced chronic pulmonary alcoholization, the ethanol consumption in mice was similar to that of
when access to 10% (v/v) ethanol solution was given. In contrast, when
mice had access to both drinking bottles, i.e. free choice, their ethanol preference was significantly lower than
mice when expressed as percentage of total consumption. This result is in agreement with our previous study in Wistar rats of the action of the CB1 cannabinoid receptor inhibitor SR 141716 (Lallemand and De Witte, 2001
) and data reported recently by Hungund et al. (2003)
, Poncelet et al. (2003)
, Racz et al. (2003)
, Wang et al. (2003)
and Naassila et al. (2004)
, which show that a CB1 receptor antagonist decreases ethanol consumption in rats and mice. Nevertheless, when ethanol preference is expressed as g/kg body weight/day,
mice presented significant ethanol intake time point higher than
mice.
In both non-forced alcoholized and chronically forced alcoholized experiment, the mice showed a significantly lower weight than the
mice. This result was in contradiction to the results from a previous study (Wang et al., 2003
) where no difference was observed when the animals had free access to the food. A weight difference between
and
mice has been described between gender (Hungund et al., 2003
) when there is restricted food access. In another study,
mice gained less weight than
mice when fed with high fat diet (Ravinet-Trillou et al., 2003
). Conversely, these data could be interpreted as a higher weight gain by
mice, which is in accordance with the results of Wang et al. (2003)
, although in our experiments the mice had full access to the food. This effect could be due to the length of the experiment and the presence of ethanol, which modulates endocannabinoid levels in neuronal cells (Gonzalez et al., 2002
).
Both CB1 genotypes showed no significant differences in their motility irrespective of whether they were chronically forced alcoholized or not. There was also no difference in motilities before and after chronic alcoholization. These results are in agreement with those observed in the study of Racz et al. (2003) where
mice showed no withdrawal symptoms when compared with
mice. In contrast, Naassila et al. (2004)
reported an increased ethanol withdrawal severity in
mice. This discrepancy in the results obtained in those studies may be caused by the use of different measures for alcohol withdrawal symptoms.
In conclusion, these data showed: (1) a higher BEC in mice after a high acute ethanol dose of 5 g/kg; (2) during forced chronic pulmonary alcoholization, higher BEC levels are reached at an earlier time point in
mice, and (3)
mice show a lower ethanol preference. These results strongly support an important role for the endocannabinoidCB1 receptor system in ethanol drinking behaviour as well as other actions of ethanol. Further studies of enzymes involved in the pharmacokinetics of ethanol are needed to explain the apparent differences in ethanol absorption/distribution observed in
mice after high doses of ethanol.
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ACKNOWLEDGEMENTS |
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REFERENCES |
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Aufrère, G., Le Bourhis, B. and Beaugé, F. (1997) Ethanol intake after chronic intoxication by inhalation of ethanol vapour in rats: behavioural dependence. Alcohol 14, 247253.[CrossRef][ISI][Medline]
Basavarajappa, B. S., and Hungund, B. L. (1999a) Down-regulation of cannabinoid receptor agonist-stimulated [35S] GTPcS binding in synaptic plasma membrane from chronic ethanol exposed mouse. Brain Research 815, 8997.[CrossRef][ISI][Medline]
Basavarajappa, B. S. and Hungund, B. L. (1999b) Chronic ethanol increases the cannabinoid receptor agonist, anandamide and its precursor N-arachidonyl phosphatidyl ethanolamine in SK-N-SH cells. Journal of Neurochemistry 72, 522528.[CrossRef][ISI][Medline]
Basavarajappa, B. S. and Hungund, B. L. (2002) Neuromodulatory role of the endocannabinoid signaling system in alcoholism: an overview. Prostaglandins, Leukotrienes and Essential Fatty Acids 66, 287299.[CrossRef][ISI][Medline]
Basavarajappa, B. S., Cooper, T. B. and Hungund, B. L. (1998) Chronic ethanol administration down-regulates cannabinoid receptors in mouse brain synaptic plasma membrane. Brain Research 793, 212218.[CrossRef][ISI][Medline]
Basavarajappa, B. S., Saito, M., Cooper, T. B. and Hungund, B. L. (2000) Stimulation of cannabinoid receptor agonist 2-arachidonylglycerol by chronic ethanol and its modulation by specific neuromodulators in cerebellar granule neurons. Biochimica et Biophysica Acta 1535, 7886.[ISI][Medline]
Batkai, S., Jarai, Z., Wagner, J. A. et al. (2001) Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. Nature Medicine 7, 827832.[CrossRef][ISI][Medline]
Bouaboula, M., Rinaldi, M., Carayon, P., Carrilon, C., Delpech, B., Shire, D., Le Fur, G. and Casellas, P. (1993) Cannabinoid receptor expression in human leucocytes. European Journal of Biochemistry 214, 173180.[Abstract]
Bruguerolle, B., Attolini, L., Roucoules, X. and Lorec, A. M. (1994) Cigarette smoke increases bupivacaine metabolism in rats. Canadian Journal of Anaesthesia 41, 733737.[ISI][Medline]
Bruguerolle, B. and Dubus, J. C. (1993) Fever-induced changes in theophylline pharmacokinetics in rats. Fundamental and Clinical Pharmacology 7, 429433.[ISI][Medline]
Colombo, G., Agabio, R., Fa, M., Guano, L., Lobina, C., Loche, A., Reali, R. and Gessa, G. (1998) Reduction of voluntary ethanol intake in ethanol-preferring sP rats by the cannabinoid antagonist SR-141716. Alcohol and Alcoholism 33, 126130.[Abstract]
Colombo, G., Serra, S., Brunetti, G., Gomez, R., Melis, S., Vacca, G., Carai, M. A. M. and Gessa, G. L. (2002) Stimulation of voluntary ethanol intake by cannabinoid receptor agonists in ethanol preferring sP rats. Psychopharmacology 159: 181187.[CrossRef][ISI][Medline]
Devane, W. A., Hanus, L., Breuer, A. et al. (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258, 19461949.[ISI][Medline]
Di Marzo, V., Goparaju, S. K., Wang, L. et al. (2001) Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 410, 822825.[CrossRef][ISI][Medline]
Facci, L., Dal Toso, R., Romanello, S., Buriani, A., Skaper, S. D. and Leon, A. (1995) Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proceeding of National Academy of Science of the United States of America 92, 33763380.[ISI]
Finn, D. A. and Crabbe, J. C. (1999) Chronic ethanol differentially alters susceptibility to chemically induced convulsions in withdrawal seizure-prone and -resistant mice. Journal of Pharmacology and Experimental Therapeutics 288, 782790.
Freedland, C. S., Sharpe, A. L., Samson, H. H. and Porrino, L. J. (2001) Effects of SR141716A on ethanol and sucrose self-administration. Alcoholism: Clinical and Experimental Research 25, 277282.[ISI][Medline]
Gallate, J. E. and McGregor, I. S. (1999) The motivation for beer in rats: effects of ritanserin, naloxone and SR 141716. Psychopharmacology 142, 302308.[CrossRef][ISI][Medline]
Gallate, J. E., Saharov, T., Mallet, P. E. and McGregor, I. S. (1999) Increased motivation for beer in rats following administration of a cannabinoid CB1 receptor agonist. European Journal of Pharmacology 370, 233240.[CrossRef][ISI][Medline]
Gonzalez, S., Fernandez-Ruiz, J., Sparpaglione, V., Parolaro, D. and Ramos, J. A. (2002) Chronic exposure to morphine, cocaine or ethanol in rats produced different effects in brain cannabinoid CB1 receptor binding and mRNA levels. Drug and Alcohol Dependence 66, 7784.[CrossRef][ISI][Medline]
Herkenham, M., Lynn, A. B., Johnson, M. R., Melvin, L. S., de Costa, B. R. and Rice, K. C. (1991) Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiography study. Journal of Neuroscience 11, 563583.[Abstract]
Hettiarachchi, K., Green, C. E., Ramanathan-Girish, S., Wu, B., Jackson, C. J., Ridge, S., Salem, M. A. and Lanser, M. E. (2001) Analysis of 2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(3-iodo-E-allyl)nortropane in rat plasma. II. Pharmacokinetic profile in male and female Sprague-Dawley rats evaluated by capillary electrophoresis. Journal of Chromatography A 924, 471481.[CrossRef][ISI][Medline]
Hungund, B. L. and Basavarajappa, B. S. (2000a) Are anandamide and cannabinoid receptors involved in ethanol tolerance? A review of the evidence. Alcohol and Alcoholism 35, 126133.
Hungund, B. L. and Basavarajappa, B. S. (2000b) Role of brain's own marijuana, anandamide and its cannabinoid receptors (CB1) in alcoholism. In Recent Research Development in Neurochemistry, Vol. 3, Pandalai R. S. ed., pp. 926. Research Signpost Trivandrum, India.
Hungund, B. L., Basavarajappa, B. S., Vadasz, C., Kunos, G., Rodríguez de Fonseca, F., Colombo, G., Serra, S., Parsons, L. and Koob, G. F. (2002) Ethanol, endocannabinoids and cannabinoidergic signaling system. Alcoholism: Clinical and Experimental Research 26, 565574.[ISI][Medline]
Hungund, B. L., Szakall, I., Adam, A., Basavarajappa, B. S. and Vadasz, C. (2003) Cannabinoid CB1 receptor knockout mice exhibit markedly reduced voluntary alcohol consumption and lack alcohol-induced dopamine release in the nucleus accumbens. Journal of Neurochemistry 84, 698704.[CrossRef][ISI][Medline]
Kishimoto, R., Fujiwara, I., Kitayama, S., Goda, K., and Nakata, Y. (1995) Changes in hepatic enzyme activities related to ethanol metabolism in mice following chronic ethanol administration. Journal of Nutritional Science and Vitaminology 41, 527543.[ISI][Medline]
Lallemand, F. and De Witte, P. (2001) The effects of CB1 cannabinoid receptor blockade on ethanol preference after chronic ethanol administration, Alcoholism: Clinical and Experimental Research 25, 13171323.[CrossRef][ISI][Medline]
Lallemand, F., Soubrié, P. and De Witte, P. (2004) Effects of CB1 Cannabinoid Receptor Blockade on Ethanol Preference after One or Two Chronic Ethanol Re-exposure and withdrawals. Alcohol and Alcoholism, doi:10.1093/alalc/agh098.
Le Bourhis, B. (1975) Alcoolisation du rat par voie pulmonaire. Comptes Rendus des Séances de la Société de Biologie et de ses filiales 169, 898904.[ISI][Medline]
Le Bourhis, B. (1977) Sur l'établissement de la dépendance des rats à l'égard de l'alcool. Physiology and Behaviour 18, 475478.[CrossRef][ISI]
Ledent, C., Valverde, O., Cossu, G., Petitet, F., Aubert, J.-F., Beslot, F., Böhme, G. A., Imperato, A., Pedrazzini, T., Roques, B. P., Vassart, G., Fratta, W. et al. (1999) Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science 283, 401404.
Lévénès, C., Daniel, H., Soubrié, P. and Crépel, F. (1998) Cannabinoids decrease excitatory transmission and impair long-term depression in rat cerebellar Purkinje cells. Journal of Physiology, 510, 867879.
Lieber, C. S. (1999) Microsomal ethanol-oxidizing system (MEOS): the first 30 years (19681998)a review. Alcoholism: Clinical and Experimental Research 23, 9911007.[ISI][Medline]
Mechoulam, R., Ben-Shabat, S., Hanus, L. et al. (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochemical Pharmacology 50, 8390.[CrossRef][ISI][Medline]
Mechoulam, R. and Fride, E. (1995) The unpaved road to the endogenous brain cannabinoid ligands, the anandamides. In Cannabinoid Receptors, Pertwee, R. G. ed., pp. 233258. Academic Press, London.
Munro, S., Thomas, K. L. and Abu-Shaar, M. (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365, 6165.[CrossRef][ISI][Medline]
Naassila, M., Pierrefiche, O., Ledent, C. and Daoust, M. (2004) Decreased alcohol self-administration and increased alcohol sensitivity and withdrawal in CB1 receptor knockout mice. Neuropharmacology 46, 243253.[CrossRef][ISI][Medline]
Navarro, M., Chowen, J., Carrera, M. R. A., del Arco, I., Villanúa, M. A., Martin, Y., Roberts, A. J., Koob, G. F. and Rodríguez de Fonseca, F. (1998) CB1 cannabinoid receptor antagonist-induced opiate withdrawal in morphine-dependent rats, Neuroreport 9, 33973402.[ISI][Medline]
Ortiz, S., Oliva, J. M., Perez-Rial, S., Palomo, T. and Manzanares, J. (2004) Chronic ethanol consumption regulates cannabinoid CB1 receptor gene expression in selected regions of rat brain. Alcohol and Alcoholism 39, 8892.
Pertwee, R. G. (2001) Cannabinoids and the gastrointestinal tract. Gut 48, 859867.
Poncelet, M., Maruani, J., Calassi, R. and Soubrie, P. (2003) Overeating, alcohol and sucrose consumption decrease in CB1 receptor deleted mice. Neuroscience Letters 343, 216218.[CrossRef][ISI][Medline]
Racz, I., Bilkei-Gorzo, A., Toth, Z. E., Michel, K., Palkovits, M. and Zimmer, A. (2003) A critical role for the cannabinoid CB1 receptros in alcohol dependence and stress-stimulated ethanol drinking. Journal of Neuroscience 23, 24532458.
Ravinet-Trillou, C., Arnone, M., Delgorge, C., Gonalons, N., Keane, P., Maffrand, J. P. and Soubrié, P. (2003) Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. American Journal of Physiology 284, 345353.
Robbe, D., Kopf, M., Remaury, A., Bockaert, J. and Manzoni, O. J. (2002) Endogenous cannabinoids mediate long-term synaptic depression in the nucleus accumbens. Proceedings of the National Academy of Science of the United States of America 99, 83848388.
Rodríguez de Fonseca, F., Roberts, A. J., Bilbao, A. and Koob, G. F. (1999) Cannabinoid receptor antagonist SR141716A decreases operant ethanol self administration in rats exposed to ethanol-vapor chambers. Zhongguo Yao Li Xue Bao 20, 11091114.[ISI][Medline]
Serra, S., Brunetti, G., Pani, M., Vacca, G., Carai, M. A. M., Gessa, G. L. and Colombo, G. (2002) Blockade by cannabinoid CB1 receptor antagonist, SR141716, of alcohol deprivation effect in alcohol-preferring rats. European Journal of Pharmacology 443, 9597.[CrossRef][ISI][Medline]
Shire, D., Calandra, B., Bouaboula, M., Barth, F., Rinaldi-Carmona, M., Casellas, P. and Ferrara, P. (1999) Cannabinoid receptor interactions with the antagonists SR 141716A and SR 144528. Life Science 65, 627635.[CrossRef][ISI][Medline]
Stella, N., Schweitzer, P. and Piomelli, D. (1997) A second endogenous cannabinoid that modulates long-term potentiation. Nature 388, 773778.[CrossRef][ISI][Medline]
Terdal, E. S. and Crabbe, J. C. (1994) Indexing withdrawal in mice: Matching genotypes for exposure in studies using ethanol vapor inhalation. Alcoholism: Clinical and Experimental Research 18, 542547.[ISI][Medline]
Wang, L., Liu, J., Harvey-White, J., Zimmer, A. and Kunos, G. (2003) Endocannabinoid signalling via cannabinoid receptor 1 is involved in ethanol preference and its age dependent decline in mice. Proceedings of National Academy of Science of the United States of America 100, 13931398.[CrossRef][ISI]
Zimmer, A., Hohmann, A., Herkenham, M. and Bonner, T. (1999) Increased mortality, hypoactivity and hypoalgesia in cannabinoid CB1 receptor knockout mice. Proceedings of National Academy of Science of the United States of America 96, 57805785.[CrossRef][ISI]
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