Is ethanol a pro-drug? The role of acetaldehyde in the central effects of ethanol

[en] Acetaldehyde, the first product of ethanol metabolism, has been speculated to be involved in many behavioral effects of ethanol. However, its precise role remains a matter of debate, with some researchers suggesting that acetaldehyde has no role in the effects of ethanol and others contending that ethanol is a pro-drug whose pharmacological action is mediated by acetaldehyde. Recent studies support a role for acetaldehyde in the stimulant, reinforcing, hypnotic and amnesic effects of ethanol, and, in particular, alcohol abuse and alcoholism. However, current evidence indicates that acetaldehyde is not involved in some of the major neurochemical effects of ethanol. It is therefore likely that ethanol and acetaldehyde molecules act synergistically to determine the multiple neurochemical and behavioral effects of alcohol consumption.

Research Center/Unit :

Centre de Neurosciences Cognitives et Comportementales - ULiège

Disciplines :

Pharmacy, pharmacology & toxicology
Psychiatry
Neurosciences & behavior

Author, co-author :

Quertemont, Etienne ; Université de Liège - ULiège > Département des sciences cognitives > Psychologie quantitative

Tambour, Sophie ; Université de Liège - ULiège > Département des sciences cognitives > Neuroscience comportementale et psychopharmacologie expér.

Language :

English

Title :

Is ethanol a pro-drug? The role of acetaldehyde in the central effects of ethanol

Publication date :

2004

Journal title :

Trends in Pharmacological Sciences

ISSN :

0165-6147

eISSN :

1873-3735

Publisher :

Elsevier Science London, London, United Kingdom

Volume :

Issue :

Pages :

130-134

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique

Available on ORBi :

since 21 January 2009

Statistics

Number of views

89 (4 by ULiège)

Number of downloads

4 (1 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

McBride W.J., et al. Involvement of acetaldehyde in alcohol addiction. Alcohol. Clin. Exp. Res. 26:2002;114-119.
Quertemont E., De Witte P. Conditioned stimulus preference after acetaldehyde but not ethanol injections. Pharmacol. Biochem. Behav. 68:2001;449-454.
Rodd-Henricks Z.A., et al. The reinforcing effects of acetaldehyde in the posterior ventral tegmental area of alcohol-preferring rats. Pharmacol. Biochem. Behav. 72:2002;55-64.
Tampier L., Quintanilla M.E. Effect of acetaldehyde on acute tolerance and ethanol consumption in drinker and nondrinker rats. J. Stud. Alcohol. 63:2002;257-262.
Quintanilla M.E., et al. Aversion to acetaldehyde: differences in low-alcohol-drinking (UchA) and high-alcohol-drinking (UchB) rats. Alcohol. 26:2002;69-74.
Escarabajal M.D., et al. Role of acetaldehyde in ethanol-induced conditioned taste aversion in rats. Psychopharmacology (Berl.). 167:2003;130-136.
Grigson P.S., Twining R.C. Cocaine-induced suppression of saccharin intake: a model of drug-induced devaluation of natural rewards. Behav. Neurosci. 116:2002;321-333.
Quertemont E., et al. Role of catalase in ethanol-induced conditioned taste aversion: a study with 3-amino-1,2,4-triazole. Drug Alcohol Depend. 70:2003;77-83.
Correa M., et al. Locomotor stimulant effects of intraventricular injections of low doses of ethanol in rats: acute and repeated administration. Psychopharmacology (Berl.). 170:2003;368-375.
Arizzi M.N., et al. Behavioral effects of intraventricular injections of low doses of ethanol, acetaldehyde, and acetate in rats: studies with low and high rate operant schedules. Behav. Brain Res. 147:2003;203-210.
Correa M., et al. Open field locomotor effects in rats after intraventricular injections of ethanol and the ethanol metabolites acetaldehyde and acetate. Brain Res. Bull. 62:2003;197-202.
Correa M., et al. Brain catalase activity is highly correlated with ethanol-induced locomotor activity in mice. Physiol. Behav. 73:2001;641-647.
Escarabajal M.D., Aragon C.M.G. Concurrent administration of diethyldithiocarbamate and 4-methylpyrazole enhances ethanol-induced locomotor activity: the role of brain ALDH. Psychopharmacology (Berl.). 160:2002;339-343.
Pastor R., et al. Ethanol-stimulated behaviour in mice is modulated by brain catalase activity and H2O2 rate of production. Psychopharmacology (Berl.). 165:2002;51-59.
Escarabajal M.D., Aragon C.M.G. The effect of cyanamide and 4-methylpyrazole on the ethanol-induced locomotor activity in mice. Pharmacol. Biochem. Behav. 72:2002;389-395.
Nishiguchi M., et al. Different blood acetaldehyde concentration following ethanol administration in a newly developed high alcohol preference and low alcohol preference rat model. Alcohol Alcohol. 37:2002;9-12.
Isse T., et al. Diminished alcohol preference in transgenic mice lacking aldehyde dehydrogenase activity. Pharmacogenetics. 12:2002;621-626.
Peng G.S., et al. Involvement of acetaldehyde for full protection against alcoholism by homozygosity of the variant allele of mitochondrial aldehyde dehydrogenase gene in Asians. Pharmacogenetics. 9:1999;463-476.
Zimatkin S.M., et al. Relationship of brain ethanol metabolism to the hypnotic effect of ethanol. I: Studies in outbred animals. Alcohol. Clin. Exp. Res. 25:2001;976-981.
Zimatkin S.M., et al. Relationship of brain ethanol metabolism to the hypnotic effect of ethanol. II: Studies in selectively bred rats and mice. Alcohol. Clin. Exp. Res. 25:2001;982-988.
Quertemont E., Grant K.A. Role of acetaldehyde in the discriminative stimulus effects of ethanol. Alcohol. Clin. Exp. Res. 26:2002;812-817.
Quertemont E. Discriminative stimulus effects of ethanol with a conditioned taste aversion procedure: lack of acetaldehyde substitution. Behav. Pharmacol. 14:2003;343-350.
Mascia M.P., et al. Does acetaldehyde mediate ethanol action in the central nervous system? Alcohol. Clin. Exp. Res. 25:2001;1570-1575.
Di Chiara G. Nucleus accumbens shell and core dopamine: differential role in behavior and addiction. Behav. Brain Res. 137:2002;75-114.
Foddai, M. et al. Acetaldehyde increases dopaminergic neuronal activity in the VTA. Neuropsychopharmacology (in press).
Naoi M., et al. Dopamine-derived salsolinol derivatives as endogenous monoamine oxidase inhibitors: occurrence, metabolism and function in human brains. Neurotoxicology. 25:2004;193-204.
Jamal M., et al. In vivo study of salsolinol produced by a high concentration of acetaldehyde in the striatum and nucleus accumbens of free-moving rats. Alcohol. Clin. Exp. Res. 27:2003;79S-84S.
Jamal M., et al. In vivo formation of salsolinol induced by high acetaldehyde concentration in rat striatum employing microdialysis. Alcohol Alcohol. 38:2003;197-201.
Rodd Z.A., et al. Salsolinol produces reinforcing effects in the nucleus accumbens shell of alcohol-preferring (P) rats. Alcohol. Clin. Exp. Res. 27:2003;440-449.
Ward R.J., et al. Acetaldehyde-induced changes in the monoamine and amino acid extracellular microdialysate content of the nucleus accumbens. Neuropharmacology. 36:1997;225-232.