IN VIVO FORMATION OF SALSOLINOL INDUCED BY HIGH ACETALDEHYDE CONCENTRATION IN RAT STRIATUM EMPLOYING MICRODIALYSIS

Mostofa Jamal*, Kiyoshi Ameno, Takako Kubota, Setsuko Ameno, Xia Zhang, Mitsuru Kumihashi and Iwao Ijiri

Department of Forensic Medicine, Faculty of Medicine, Kagawa Medical University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan

Received 12 March 2002; in revised form 12 August 2002; accepted 28 October 2002


    ABSTRACT
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Aims: The in vivo formation of salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquionoline), an endogeneous condensation product of dopamine (DA) with acetaldehyde (AcH), was examined following the administration of cyanamide (CY) plus ethanol (EtOH) using microdialysis-high-performance liquid chromatography with electrochemical detection. Methods: After the insertion of a microdialysis probe into the striatum, rats were treated with CY (a potent inhibitor of aldehyde dehydrogenase, 50 mg/kg), 4-methylpyrazole (4-MP, a strong inhibitor of alcohol dehydrogenase, 82 mg/kg), and CY + 4-MP, followed 1 h later by EtOH (1 g/kg), CY and 4-MP only by intraperitoneal administration. Results: In the CY + EtOH group, salsolinol was detected in striatal dialysates and high AcH concentrations were found in the blood. The time course of changes in salsolinol concentrations correlated with blood AcH concentrations. In the other experimental groups, salsolinol in the dialysates and high AcH concentrations in the blood were not detected. Conclusions: These observations indicate that: (1) high AcH concentrations induce the formation of salsolinol in the rat striatum; (2) there is no effect of EtOH or AcH on striatal dialysate concentrations of DA and 5-hydroxytryptamine.


    INTRODUCTION
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquionoline), a dopamine (DA)-derived alkaloid, is naturally present in the rat brain (Sjoquist and Magnusson, 1980Go) as well as in the human brain (Sjoquist et al., 1982Go), and salsolinol is also found in certain foods, such as cheese and banana (Riggin et al., 1976Go) and in some alcoholic beverages such as beer and wine (Duncan and Smythe, 1982Go). Salsolinol levels have been reported to be increased in human urine (Michael et al., 1979Go) and cerebrospinal fluid (Sjoquist et al., 1985Go) after alcohol ingestion. It is also found in the striatum of rats following intraperitoneal administration of calcium carbimide [CC, a strong inhibitor of aldehyde dehydrogenase (ALDH) activity] plus ethanol (EtOH) (Brien et al., 1983Go). Salsolinol has several unique pharmacological activities, including: (1) inhibition of the active uptake of catecholamines into nerve terminals; (2) release of stored catecholamines; (3) inhibition of monoamine oxidase (MAO), catechol-O-methyl transferase (COMT), and tyrosine hydroxylase activator (Heikkila et al., 1971Go; Giovine et al., 1976Go; Weiner and Collins, 1978Go). Its neuropharmacological effects depend on several factors, including the preferred accumulation site in the brain, the speed of biotransformation, and the propensity to form oxygen free radicals. Under certain circumstances, biogenic amines, particularly DA, may be diverted from their normal metabolism through irreversible condensation with aldehydes or {alpha}-keto acids. However, salsolinol is formed in vivo through a non-enzymatic ring cyclization of DA with acetaldehyde (AcH).

AcH, the first metabolite of EtOH, is formed by the oxidation of EtOH, which is catalysed primarily by alcohol dehydrogenase (ADH) in the liver. AcH is a highly reactive compound, which can produce several neurochemical, behavioural and neurotoxic effects. It can adversely alter normal brain function by: (1) altering cellular function (Tabakoff et al., 1976Go); (2) altering the metabolism of biogenic amines (Truitt and Walsh, 1971Go); (3) forming adducts with neurotransmitters (Israel et al., 1986Go); (4) generating bioactive derivatives, such as tetrahydroisoquinolones and tetrahydropapaverine, after interaction with catecholamines (Bardsley and Tipton, 1980Go). Genetically, a high accumulation of AcH may occur in the blood of some Asian populations with lower ALDH activity following EtOH ingestion, which may lead to individual discomfort and aversion to alcohol (Enomoto et al., 1991Go).

Several in vitro and in vivo studies have suggested that AcH is formed by EtOH in the brain. Tabakoff et al.(1976)Go reported that all AcH that enters the brain is metabolized by ALDH when blood levels are below 70 µM. Sippel (1974)Go noted that very high AcH concentrations (>50 µM) are needed in the blood before it can be detected in the brain. Another study by Westcott et al.(1980)Go demonstrated that blood and brain levels of AcH were significantly correlated in rats treated with an ALDH inhibitor followed by EtOH. Heap et al.(1995)Go argued that the circulating blood concentration of AcH was similar to that in the brain, and that AcH readily crosses the blood–brain barrier. In contrast, Zimatkin (1991)Go and Zimatkin et al.(1998)Go found that blood AcH derived from the peripheral metabolism of EtOH penetrates into the brain with difficulty, due to the presence of a high concentration of ALDH at the blood–brain barrier. Furthermore, it has been reported that EtOH is metabolized in vitro to AcH primarily by catalase in the brain (Gill et al., 1992Go; Zimatkin et al., 1998Go).

We investigated the in vivo formation of salsolinol in the rat striatum under conditions involving high AcH concentrations and the effects of EtOH and AcH on striatal dialysates of DA and also 5-hydroxytryptamine (5-HT) in freely moving rats after various treatments.


    MATERIALS AND METHODS
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Animals
Male Wistar rats (8–10 weeks old and weighing 250–300 g) were used throughout the study. Rats were housed in stainless-steel cages with ad libitum access to standard laboratory food and tap water and were maintained in a controlled environment with respect to temperature (23°C), relative humidity (50–70%) and light/dark cycle (12 h/12 h). All experimental procedures were approved ethically by the Kagawa Medical University Animal Investigation Committee.

Reagents
Cyanamide (CY) and DA were purchased from Wako Pure Chemical Industries (Japan). Salsolinol, 5-HT and 4-methylpyrazole (4-MP) were purchased from Sigma Chemical Gmbh (Germany), and all other reagents used were the highest pure-grades available.

Microdialysis technique
After anaesthetizing each rat with pentobarbital-Na (50 mg/kg, intraperitoneally), the skull was exposed and a small hole was drilled to allow implantation of a guide cannula (8 mm long; AG-8, Eicom, Japan) into the rat striatum. Stereotaxic coordinates with respect to the microdialysis probe tip were as follows: anterior, 0.2 mm to the bregma; lateral, 3 mm; height, 3 mm below the dura (Paxinos and Watson, 1986Go). The guide cannula was anchored firmly to the skull surface in each rat by dental cement, and then a dummy cannula was inserted through the guide cannula for 1 day. A concentric dialysis probe (8 mm long, A-I-8–3, Eicom) with an active dialysis membrane (3 mm long, i.d. 0.20 mm, o.d. 0.22 mm, cut-off value 50 kDa) constructed from hemicellulose dialysis tubing was inserted into the guide cannula on the day of experimentation in unanaesthetized and freely moving rats. Ringer’s solution (147 mM NaCl, 4 mM KCl, 2.25 mM CaCl2) was perfused continually through the probe’s inlet at a constant flow rate of 0.8 µl/min during microdialysis. The animals were deprived of food throughout microdialysis.

Experimental groups
Six experimental groups were used in the present study: (1) a control group (EtOH, 1 g/kg); (2) CY alone; (3) CY + EtOH; (4) CY + 4-MP + EtOH; (5) 4-MP + EtOH; (6) 4-MP alone. Rats received an intraperitoneal injection of EtOH [20% (v/v), 1 g/kg] 1 h after administration of CY (50 mg/kg), 4-MP (82 mg/kg), or both.

High-performance liquid chromatographic (HPLC) conditions
Simultaneous quantification of DA, 5-HT and salsolinol in dialysate samples was performed using Eicom HPLC systems equipped with an electrochemical detector (ECD-300, Eicom) and an autosampler (EAS-20, Eicom). The perfused dialysates were collected every 5 min. The main operative conditions of HPLC were as follows: column (Eicom-PAK PP-ODS; 4.6 x 30 mm), oven temperature 25°C, detector, oxidation potential (+400 mV versus an Ag/AgCl reference analytical electrode), mobile phase: 0.1 M phosphate buffer [mixture of NaH2PO4 (15.6 g/l) and Na2HPO4 (14.2 g/l) solution, 100:16, pH 6], methanol (1%, v/v), EDTA-Na2 (50 mg/l), and decanesulphonate-Na (500 mg/l) at a flow rate of 0.5 ml/min. Injections were automatically performed onto the analytical column during the experimental period. The perfused dialysates were collected every 5 min by an autoinjector connected to an automated HPLC-ECD, and chromatograms were recorded with a chromatocorder 21 (Tosoh, Japan).

Quantification of EtOH and AcH
Quantification of EtOH and AcH in the blood were performed by the head-space GC method, according to our previous report (Kinoshita et al., 1995Go).

Histology
At the end of microdialysis, the rats were deeply anaesthetized by pentobarbital-Na and decapitated. The brains were removed for histological verification of the tip location of the probes by visual inspection under the dissecting microscope.

Statistical analysis
A statistical program of StatView (J-4.5; USA) was used for data analysis. Values are expressed as means ± SD. Statistical analysis of data was performed using Student’s t-test. Values of P < 0.05 were accepted as representing significant differences.


    RESULTS
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
All measurements were conducted when the steady states of DA and 5-HT were achieved following the insertion of the microdialysis probe through the guide cannula. Figure 1Go shows chromatograms obtained by the HPLC-ECD analysis of the striatal dialysates of (A) control (EtOH, 1 g/kg), (B) the rats treated with CY (50 mg/kg) 1 h after EtOH, and (C) a pure sample of salsolinol. In the rats treated with CY + EtOH, an additional peak with a retention time of about 1.8 min, was detected, which was not seen in controls or in other experimental groups (chromatograms not shown). The retention time of the unknown peak was identical to that of the salsolinol, as detected in a pure sample. In all the experimental groups, DA and 5-HT were detected at a retention time of approximately 1.7 and 3.8 min, respectively.



View larger version (11K):
[in this window]
[in a new window]
 
Fig. 1. HPLC chromatograms. Chromatograms were obtained by striatal dialysates of the control (EtOH, 1 g/kg) group (A); the experimental group treated with CY (50 mg/kg), then 1 h later by EtOH (B); and with a pure sample of salsolinol (1 pg/ml) (C). 5-HT, 5-hydroxytryptamine.

 
Figure 2Go shows the time course of changes in the extracellular levels of DA and 5-HT in the dialysates (A) and in the blood concentrations of EtOH and AcH (B) in the EtOH group. The dialysate levels of DA and 5-HT at 1 h were 1.07 ± 0.07 and 0.52 ± 0.05 (means ± SD) pg/µl, respectively; the values did not change significantly following EtOH administration. No salsolinol was detected in this group. The blood levels of EtOH at 1 h after injection were 17.5 ± 2.6 mM (mean ± SD) and thereafter gradually decreased. AcH levels were negligible by comparison with those of EtOH.



View larger version (20K):
[in this window]
[in a new window]
 
Fig. 2. Time course of changes in the dialysate levels of DA and 5-HT (A) and in the blood concentrations of EtOH and AcH (B) in rats treated with EtOH. Values represent the means ± SD (n = 3). DA, dopamine; 5-HT, 5-hydroxytryptamine; EtOH, ethanol; AcH, acetaldehyde., EtOH (1 g/kg) intraperitoneal injection time.

 
Figure 3Go shows the time course of changes in the extracellular levels of DA, 5-HT, and salsolinol in the dialysates (A) and in the blood concentrations of EtOH and AcH in the CY + EtOH group (B). The striatal salsolinol levels in the dialysates were 0.13 ± 0.067 (mean ± SD) pg/µl at 30 min after an EtOH dose, which reached a maximum of 0.34 ± 0.057 (mean ± SD) pg/µl at 1 h and thereafter gradually decreased. Salsolinol was not detected at 4 h after EtOH injection. The dialysate levels of DA and 5-HT at 1 h were 0.94 ± 0.13 and 0.39 ± 0.3 (mean ± SD) pg/µl, respectively, and did not change significantly following EtOH administration. The peak blood concentrations of EtOH (25.4 ± 3.4 mM, mean ± SD) and AcH (28.22 ± 5.3 µM, mean ± SD) reached a maximum at 1 h after EtOH dosing and then gradually decreased. No AcH was observed in the blood at 4 h after EtOH injection. The blood AcH concentrations correlated well with the dialysate levels of salsolinol in the striatum.



View larger version (25K):
[in this window]
[in a new window]
 
Fig. 3. Time course of changes in the dialysate levels of DA, 5-HT and salsolinol (A) and in the blood concentrations of EtOH and AcH (B) in rats treated with cyanamide and EtOH. Values represent the means ± SD (n = 3). DA, dopamine; 5-HT, 5-hydroxytryptamine; EtOH, ethanol; AcH, acetaldehyde. , CY (50 mg/kg), , EtOH (1 g/kg) intraperitoneal injection time.

 
Table 1Go shows the dialysate levels of DA, 5-HT and salsolinol as well as the blood concentrations of EtOH and AcH 1 h after EtOH administration in the EtOH (control), CY + EtOH, CY + 4-MP + EtOH and 4-MP + EtOH groups. Salsolinol was detected only in the CY + EtOH group, and AcH was observed in both the EtOH (control) and CY + EtOH groups. No significant changes were observed in the dialysate levels of DA and 5-HT in the above-mentioned groups (Table 1Go). In the CY and 4-MP groups, DA and 5-HT levels also did not change significantly (data not shown). The highest blood level of AcH was observed in the CY + EtOH groups only.


View this table:
[in this window]
[in a new window]
 
Table 1. Microdialysate levels of dopamaine (DA), 5-hydroxytryptamine (5-HT) and salsolinol (SAL) in striatum and blood concentrations of ethanol (EtOH) and acetaldehyde (AcH) in different groups of rats
 

    DISCUSSION
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Previous chromatographic studies of salsolinol involved GLC-ECD (Brien et al., 1983Go), and GC-MS (Myers et al., 1985bGo) of the rat and HPLC-ECD (Sasaoka and Kaneda, 1988Go; Musshoff et al., 1999Go) of the human brain. Non-radioactively labelled salsolinol and DA were used for these measurements. In our experiments, brain microdialysis was performed for the determination of levels of salsolinol and also DA and 5-HT in the rat striatum following treatment with CY + EtOH. This was a relatively simple, highly sensitive and specific technique that did not require the killing of the laboratory animal. An unknown peak observed in the HPLC chromatogram in rats treated with the ALDH inhibitor CY and EtOH was confirmed as being that of salsolinol, which had the same retention time as that of a control sample. The increase and subsequent decrease in salsolinol concentrations was accompanied by changes in AcH concentration in the brain. In the present study, we observed a high blood AcH concentration (282 µM) in rats treated with CY and EtOH. The elevated concentration of blood AcH was likely to have crossed the blood–brain barrier and accumulated in the brain, thereby causing brain ALDH to become either saturated or inhibited by CY. However, the present experiment induced the accumulation of high AcH concentrations in the blood after administration of CY followed by EtOH in rats.

In order to confirm our results, an additional series of experiments was designed, using CY + 4-MP or 4-MP with EtOH, 4-MP and CY, to investigate the release of salsolinol in the brain. In these experiments, an additional agent, 4-MP (a selective ADH inhibitor), was given to the animals and was necessary in order to alter certain behavioural and neurotoxic effects due to elevated AcH concentrations. Hence, most of the adverse effects that characterize alcohol sensitivity were efficiently attenuated by 4-MP (Kupari et al., 1983Go); this was demonstrated in cases of ALDH inhibition by CY as well as in individuals who carried the ALDH2*2 allele (Wilkin and Fortner, 1985Go). However, we did observe that the accumulation of AcH was low in rats treated with CY + 4-MP following EtOH, whereas ALDH activity was inhibited by CY.

Acute intake of EtOH had no effect on salsolinol formation in the striatum (Sjoquist et al., 1983Go). One possible explanation may be that there was not a sufficient delay following ingestion, which would have led to a disturbance in the DA status and subsequent rise in salsolinol concentrations (Myers et al., 1985aGo). A previous study has shown that the striatal salsolinol concentration increased significantly in rats exposed to AcH, whereas the DA concentrations did not differ remarkably after AcH treatment (Myers et al., 1985aGo). These data suggest that AcH is the agent responsible for salsolinol formation in the brain. Therefore, any elevation in brain salsolinol concentrations might be due to an increase in brain AcH concentration. The results of our study supports this notion. To our knowledge, the present study represents the first report on in vivo salsolinol formation in freely moving rats.

ALDH is responsible not only for the metabolism of exogenous EtOH, but also for the oxidation of biogenic aldehydes in the central nervous system and in the periphery. These aldehydes are formed through oxidative deamination of biogenic amines by monoamine oxidase. CY, a potent ALDH inhibitor in the liver, as well as in the brain (Hellstrom and Tottmar, 1982Go), was used in the present experiments. The brain inhibition may alter the metabolism of biogenic amines by promoting the formation of condensation products or by increasing the levels of biogenic aldehydes. A previous in vivo report showed that extracellular concentration of both DA and 5-HT significantly decreased in the nucleus accumbens after acute intraperitoneal injection of AcH to rats (Ward et al., 1997Go). Other authors have demonstrated, using rat models, that the DA levels in the striatum remained almost unchanged following chronic treatment with EtOH and AcH (Myers et al., 1985aGo; Matsubara et al., 1987Go) and that 5-HT levels also remained largely the same in the nucleus accumbens following acute exposure to EtOH (Heidbreder and De Witte, 1993Go). On the other hand, salsolinol itself was shown to have no effect on the levels of DA and 5-HT in the striatum following acute exogenous administration (Antkiewicz-Michaluk et al., 2000Go). In the present study, DA and 5-HT concentrations in the striatum did not significantly change. It is known that two opposing factors maintain extracellular DA concentration: (1) neuronal release of DA; and (2) subsequent uptake of DA via the DA-specific transporters. Salsolinol promotes the release of catecholamines into the nerve terminal, inhibition of reuptake of catecholamines, and inhibition of the enzymes MAO and COMT (Heikkila et al., 1971Go; Giovine et al., 1976Go; Weiner and Collins, 1978Go). Our results do not support data supporting any of these mechanisms.

In conclusion, DA-derived salsolinol concentration in the striatum correlated well with the concentration of blood AcH in the present study. Changes in salsolinol concentrations following exposure to AcH do not alter DA and 5-HT concentrations in the rat striatum.


    ACKNOWLEDGEMENTS
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
We kindly thank Professor Shigeru Hishida, Dr Hiroshi Kinoshita and Minori Nishiguchi, Hyogo University, Japan for their technical assistance. This study was supported by a Grant-in-Aid for Scientific Research (c) (grant no. 12670396) from the Ministry of Education, Science and Culture, Japan.


    FOOTNOTES
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
* Author to whom correspondence should be addressed. Back


    REFERENCES
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Antkiewicz-Michaluk, L., Romanska, I., Papla, I., Michaluk, J., Bakalarz, M., Vetulani, J., Krygowska-Wajs, A. and Szczudlik, A. (2000) Neurochemical changes induced by acute and chronic administration of 1,2,3,4 tetrahydroisoquinoline and salsolinol in dopaminergic structures of rat brain. Neuroscience 96, 59–64.[CrossRef][ISI][Medline]

Bardsley, M. E. and Tipton, K. F. (1980) Metabolic aspects of ethanol dependence and tissue damage. In Addiction and Brain Damage, Richter, D., ed., pp. 75–93. University Press, Oxford.

Brien, J. F., Andrews, P. J., Loomis, C. W. and Page, J. A. (1983) Gas-liquid chromatographic determination of salsolinol in the striatum of rat during the calcium carbimide–ethanol interaction. Canadian Journal of Physiology and Pharmacology 61, 632–640.[ISI][Medline]

Duncan, M. and Smythe, G. (1982) Salsolinol and dopamine in alcoholic beverages. Lancet i (8277), 904–905.

Enomoto, N., Takase, S., Yasuhara, M. and Takada, A. (1991) Acetaldehyde metabolism in different aldehyde dehydrogenase-2 genotypes. Alcoholism: Clinical and Experimental Research 15, 141–144.[ISI][Medline]

Gill, K., Menez, J. F., Lucas, D. and Deitrich, R. A. (1992) Enzymatic production of acetaldehyde from ethanol in rat brain tissue. Alcoholism: Clinical and Experimental Research 16, 910–915.[ISI][Medline]

Giovine, A., Renis, M. and Bertolino, A. (1976) In vivo and in vitro studies on the effect of tetrahydropapaveroline and salsolinol on COMT and MAO activity in rat brain. Pharmacology 14, 86–94.[ISI][Medline]

Heap, L., Ward, R. J., Abiaka, C., Dexter, D., Lawlor, M., Pratt, P., Thomson, A., Shaw, K. and Peters, T. J. (1995) The influence of brain acetaldehyde on oxidative status, dopamine metabolism and visual discrimination task. Biochemical Pharmacology 50, 263–270.[CrossRef][ISI][Medline]

Heidbreder, C. and De Witte, P. (1993) Ethanol differentially affects extracellular monoamines and GABA in the nucleus accumbens. Pharmacology, Biochemistry and Behavior 46, 477–481.[CrossRef][ISI][Medline]

Heikkila, R., Cohen, G. and Dembiec, D. (1971) Tetrahydroisoquinoline alkaloids: uptake by rat brain homogenates and inhibition of catecholamine uptake. Journal of Pharmacology and Experimental Therapeutics 179, 250–258.[ISI][Medline]

Hellstrom, E. and Tottmar, O. (1982) Effects of aldehyde dehydrogenase inhibitors on enzymes involved in the metabolism of biogenic aldehydes in rat liver and brain. Biochemical Pharmacology 31, 3899–3905.[CrossRef][ISI][Medline]

Israel, Y., Hurwitz, E., Niemela, O. and Aron, R. (1986) Monoclonal and polyclonal antibodies against acetaldehyde-containing epitopes in acetaldehyde protein adducts. Proceedings of the National Academy of Sciences of the USA 83, 7923–7927.[Abstract]

Kinoshita, H., Ijiri, I., Ameno, S., Fuke, C. and Ameno, K. (1995) Additional proof of reduction of ethanol absorption from rat intestine in vivo by high acetaldehyde concentrations. Alcohol and Alcoholism 30, 419–421.[Abstract]

Kupari, M., Lindros, K., Hillbom, M., Heikkila, J. and Ylikahri, R. (1983) Cardiovascular effects of acetaldehyde accumulation after ethanol ingestion: their modification by beta-adrenergic blockade and alcohol dehydrogenase inhibition. Alcoholism: Clinical and Experimental Research 7, 283–288.[ISI][Medline]

Matsubara, K., Fukushima, S. and Fukui, Y. (1987) A systematic regional study of brain salsolinol levels during and immediately following chronic ethanol ingestion in rats. Brain Research 413, 336–343.[CrossRef][ISI][Medline]

Michael, A. C., William, P. N., George, F. B., Gregory, T. and Clara, G. (1979) Dopamine-related tetrahydroisoquinolines: significant urinary excretion by alcoholics after alcohol consumption. Science 206, 1184–1186.[ISI][Medline]

Musshoff, F., Schmidt, P., Dettmeyer, R., Priemer, F., Wittig, H. and Madea, B. (1999) A systematic regional study of dopamine and dopamine-derived salsolinol and norsalsolinol levels in human brain areas. Forensic Science International 105, 1–11.[CrossRef][ISI][Medline]

Myers, W. D., Kim, T. N., Singer, G., Smythe, G. A. and Duncan, M. W. (1985) Dopamine and salsolinol levels in rat hypothalami and striatum after schedule-induced self injection (SISI) of ethanol and acetaldehyde. Brain Research 358, 122–128.[CrossRef][ISI][Medline]

Myers, W. D., Mackenzie, L., Kim, T. N., Singer, G., Smythe, G. A. and Duncan, M. W. (1985b) Salsolinol and dopamine in rat medial basal hypothalamus after chronic ethanol exposure. Life Sciences 36, 309–314.[CrossRef][ISI][Medline]

Paxinos, G. and Watson, C. (1986) The Rat Brain in Streotaxic Coordinates, Plate 17, 2nd edn. Academic Press, Sydney.

Riggin, R. M., McCarty, M. J. and Kissinger, P. T. (1976) Identification of salsolinol as a major dopamine metabolite in the banana. Journal of Agricultural and Food Chemistry 24, 189–191.[ISI][Medline]

Sasaoka, T. and Kaneda, N. (1988) Analysis of salsolinol in human brain using high-performance liquid chromatography with electrochemical detection. Journal of Chromatography 428, 152–155.[Medline]

Sippel, H. W. (1974) The acetaldehyde content in rat brain during ethanol metabolism. Journal of Neurochemistry 23, 451–452.[ISI][Medline]

Sjoquist, B. and Magnusson, E. (1980) Analysis of salsolinol and salsoline in biological samples using deuterium-labeled standards and GC-MS. Journal of Chromatography 183, 17–24.[CrossRef][Medline]

Sjoquist, B., Eriksson, A. and Winblad, B. (1982) Salsolinol and catecholamines in the human brain and their relation to alcoholism. Progress in Clinical Biological Research 90, 57–67.

Sjoquist, B., Perdahl, E. and Winblad, B. (1983) The effect of alcoholism on salsolinol and biogenic amines in human brain. Drug and Alcohol Dependence 12, 15–23.[CrossRef][ISI][Medline]

Sjoquist, B., Johnson, H. A. and Borg, S. (1985) The influence of acute ethanol on the catecholamine system in man as reflected in cerebrospinal fluid and urine. A new condensation product, 1-carboxysalsolinol. Drug and Alcohol Dependence 16, 241–249.[CrossRef][ISI][Medline]

Tabakoff, B., Anderson, R. A. and Ritzmann, R. G (1976) Brain acetaldehyde after ethanol administration. Biochemical Pharmacology 25, 1305–1309.[CrossRef][ISI][Medline]

Truitt, E. B. and Walsh, M. J. (1971) The role of acetaldehyde in the actions of ethanol. In The Biology of Alcoholism, Vol. 1, Kissin, B. and Begleiter, H. eds, pp. 161–195. Plenum Press, New York.

Ward, R. J., Colantuoni, C., Dahchour, A., Quertemont, E. and De Witte, P. (1997) Acetaldehyde-induced changes in monoamine and amino acid extracellular microdialysis content of the nucleus accumbens. Neuropharmacology 36, 225–232.[CrossRef][ISI][Medline]

Weiner, C. and Collins, M. (1978) Tetrahydroisoquinoline derived from catecholamines or dopa: effects on brain tyrosine hydroxylase activity. Biochemical Pharmacology 27, 2699–2703.[CrossRef][ISI][Medline]

Westcott, J. Y., Weiner, H., Shultz, J. and Myers, R. D. (1980) In vivo acetaldehyde in the brain of the rat treated with ethanol. Biochemical Pharmacology 29, 411–417.[CrossRef][ISI][Medline]

Wilkin, J. K. and Fortner, G. (1985) Cutaneous vascular sensitivity to lower aliphatic alcohols and aldehydes in Orientals. Alcoholism: Clinical and Experimental Research 9, 522–525.[ISI][Medline]

Zimatkin, S. M. (1991) Histochemical study of aldehyde dehydrogenase in the rat CNS. Journal of Neurochemistry 56, 1–11.[ISI][Medline]

Zimatkin, S. M., Liopo, A. V. and Deitrich, R. A. (1998) Distribution and kinetics of ethanol metabolism in rat brain. Alcoholism: Clinical and Experimental Research 22, 1623–1627.[ISI][Medline]





This Article
Abstract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (8)
Request Permissions
Google Scholar
Articles by Jamal, M.
Articles by Ijiri, I.
PubMed
PubMed Citation
Articles by Jamal, M.
Articles by Ijiri, I.