[en] Recent studies involved acetaldehyde, the first ethanol metabolite, in both the rewarding and aversive effects of ethanol consumption. Brain acetaldehyde is believed to originate mainly from local brain metabolism of ethanol by the enzyme catalase. Therefore, the inhibition of catalase by 3-amino-1,2,4-triazole (aminotriazole) may help to clarify the involvement of acetaldehyde in ethanol's hedonic effects. In the present study, multiple doses of both ethanol and aminotriazole were used to investigate the effects of catalase inhibition on ethanol-induced conditioned taste aversion (CTA). A separate microdialysis experiment investigated the effects of aminotriazole pretreatment on the time course of brain ethanol concentrations. Ethanol induced a dose-dependent CTA with a maximal effect after conditioning with 2.0 g/kg ethanol. Aminotriazole pretreatments dose-dependently potentiated the CTA induced by 1.0 g/kg ethanol. However, aminotriazole pretreatments did not alter the CTA induced by higher ethanol doses (1.5 and 2.0 g/kg) probably because a maximal aversion for saccharin was already obtained without aminotriazole. The results of the microdialysis experiment confirmed that the effects of aminotriazole cannot be attributed to local alterations of brain ethanol levels. The present study argues against a role for brain acetaldehyde in ethanol's aversive effects but in favor of its involvement in ethanol rewarding properties. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
Research center :
Centre de Neurosciences Cognitives et Comportementales - ULiège
Aragon C.M.G., Spivak K., Amit Z. Blockade of ethanol induced conditioned taste aversion by 3-amino-1,2,4-triazole: evidence for catalase mediated synthesis of acetaldehyde in rat brain. Life Sci. 37:1985;2077-2084.
Aragon C.M.G., Spivak K., Amit Z. Effects of 3-amino-1,2,4-triazole on ethanol induced open field activity: evidence for brain catalase mediation of ethanol's effects. Alcohol Clin. Exp. Res. 13:1989;104-108.
Aragon C.M.G., Spivak K., Amit Z. Effect of 3-amino-1,2,4-triazole on ethanol-induced narcosis, lethality and hypothermia in rats. Pharmacol. Biochem. Behav. 39:1991;55-59.
Aragon C.M.G., Rogan F., Amit Z. Ethanol metabolism in rat brain homogenates by a catalase-H2O2 system. Biochem. Pharmacol. 44:1992;93-98.
Asin K.E., Wirtshafter D., Tabakoff B. Failure to establish a conditioned place preference with ethanol in rats. Pharmacol. Biochem. Behav. 22:1985;169-173.
Brown Z.W., Amit Z., Smith B.R. Intraventricular self-administration of acetaldehyde and voluntary consumption of ethanol in rats. Behav. Neural. Biol. 28:1980;150-155.
Correa M., Miquel M., Aragon C.M.G. Lead acetate potentiates brain catalase activity and enhances ethanol-induced locomotion in mice. Pharmacol. Biochem. Behav. 66:2000;137-142.
Eriksson C.J.P. The role of acetaldehyde in the actions of alcohol. Alcohol Clin. Exp. Res. 25:2001;15S-32S.
Eriksson C.J.P., Sippel H.W. The distribution and metabolism of acetaldehyde in rats during ethanol oxidation. I. The distribution of acetaldehyde in liver, brain, blood and breath. Biochem. Pharmacol. 26:1977;241-247.
Escarabajal D., Miquel M., Aragon C.M.G. A psychopharmacological study of the relationship between brain catalase activity and ethanol-induced locomotor activity in mice. J. Stud. Alcohol. 61:2000;493-498.
Froehlich J.C., Harts J., Lumeng L., Li T.K. Differences in response to the aversive properties of ethanol in rats selectively bred for oral ethanol preference. Pharmacol. Biochem. Behav. 31:1988;215-222.
Gauvin D.V., Holloway F.A. Historical factors in the development of ethanol-conditioned place preference. Alcohol. 9:1991;1-7.
Gill K., Menez J.F., Lucas D., Deitrich R.A. Enzymatic production of acetaldehyde from ethanol in rat brain tissue. Alcohol Clin. Exp. Res. 16:1992;910-915.
Gomez F. Induction of conditioned taste aversion with a self-administered substance in rats. Brain Res. Protoc. 8:2001;137-142.
Grigson P.S. Conditioned taste aversion and drugs of abuse: a reinterpretation. Behav. Neurosci. 111:1997;129-136.
Hunt W.A. Role of acetaldehyde in the actions of ethanol on the brain - a review. Alcohol. 13:1996;147-151.
Kristenson H. How to get the best out of antabuse. Alcohol. Alcohol. 6:1995;775-783.
Myers W.D., Ng K.T., Singer G. Ethanol preference in rats with a prior history of acetaldehyde self-administration. Experientia. 40:1984;1008-1010.
Parker L.A., Corrick M.L., Limebeer C.L., Kwiatkowska M. Amphetamine and morphine produce a conditioned taste and place preference in the house musk shrew (suncus murinus). J. Exp. Psychol. Anim. Behav. Process. 28:2002;75-82.
Paxinos G., Watson C. The Rat Brain in Stereotaxic Coordinates. 1982;Academic Press, New York.
Quertemont E., De Witte P. Conditioned stimulus preference after acetaldehyde but not ethanol injections. Pharmacol. Biochem. Behav. 68:2001;449-454.
Quertemont E., Goffaux V., Vlaminck A.M., Wolf C., De Witte P. Oral taurine supplementation modulates ethanol-conditioned stimulus preference. Alcohol. 16:1998;201-206.
Quertemont E., Rios A., Macias E., De Witte P. Implication of acetaldehyde in ethanol reinforcing and discriminative effects. Alcohol. Alcohol. 36:2001;473.
Reid L.D., Hunter G.A., Beaman C.M., Hubbell C.L. Toward understanding ethanol's capacity to be reinforcing: a conditioned place preference following injections of ethanol. Pharmacol. Biochem. Behav. 22:1985;483-487.
Robinson T.E., Whishaw I.Q. Normalization of extracellular dopamine in striatum following recovery from a partial unilateral 6-OHDA lesion of the substantia nigra: a microdialysis study in freely moving rats. Brain Res. 450:1988;209-224.
Rodd-Henricks Z.A., Melendez R.I., Zaffaroni A., Goldstein A., McBride W.J., Li T.K. The reinforcing effects of acetaldehyde in the posterior ventral tegmental area of alcohol-preferring rats. Pharmacol. Biochem. Behav. 72:2002;55-64.
Smith B.R., Amit Z., Splawinsky J. Conditioned place preference induced by intraventricular infusions of acetaldehyde. Alcohol. 1:1984;193-195.
Tampier L., Quintanilla M.E., Mardones J. Effects of aminotriazole on ethanol, water, and food intake and on brain catalase in UChA and UChB rats. Alcohol. 12:1995;341-344.
Zimatkin S.M., Deitrich R.A. Ethanol metabolism in the brain. Addiction Biol. 2:1997;387-399.
Zimatkin S.M., Liopo A.V., Deitrich R.A. Distribution and kinetics of ethanol metabolism in rat brain. Alcohol Clin. Exp. Res. 22:1998;1623-1627.
