[en] Acetaldehyde is the first active breakdown product (i.e., metabolite) generated during alcohol metabolism. It has toxic properties but also exerts other actions on the body (i.e., has pharmacological properties). Recent studies have shown that the direct administration of acetaldehyde, especially into the brain, induces several effects that mimic those of alcohol. High doses of acetaldehyde induce sedative as well as movement-and memory-impairing effects, whereas lower doses produce behavioral effects (e.g., stimulation and reinforcement) that are characteristic of addictive drugs. When acetaldehyde accumulates outside the brain (i.e., in the periphery), adverse effects predominate and prevent further alcohol drinking. To investigate the role of acetaldehyde in mediating alcohol's effects, investigators have pharmacologically manipulated alcohol metabolism and the production of acetaidehyde within the body (i.e., endogenous acetaldehyde production). Studies manipulating the activity of the enzyme catalase, which promotes acetaldehyde production in the brain, suggest that acetaldehyde contributes to many behavioral effects of alcohol, especially its stimulant properties. However, it remains controversial whether acetaldehyde concentrations obtained under normal physiological conditions are sufficient to induce significant pharmacological effects. Current evidence suggests that the contribution of acetaldehyde to alcohol's effects is best explained by a process in which acetaidehyde modulates, rather than mediates, some of alcohol's effects.
Research center :
Centre de Neurosciences Cognitives et Comportementales - ULiège
ARAGON, C.M.G., AND AMIT, Z. The effect of 3-amino-1,2,4-triazole on voluntary ethanol consumption: Evidence for brain catalase involvement in the mechanism of action. Neuropharmacology 31:709-712, 1992.
ARAGON, C.M.G.; PESOLD, C.N.; AND AMIT, Z. Ethanol-induced motor activity in normal and acatalasemic mice. Alcohol 9:207-211, 1992.
ARIZZI-LAFRANCE, M.N.; CORREA, M.; ARAGON, C.M.G.; AND SALAMONE, J.D. Motor stimulant effects of ethanol injected into the substantia nigra pars reticulata: Importance of catalase-mediated metabolism and the role of acetaldehyde. Neuropsychopharmacology 31:997-1008, 2006.
BELLUZZI, J.D.; WANG, R.; AND LESLIE, F.M. Acetaldehyde enhances acquisition of nicotine self-administration in adolescent rats. Neuropsychopharmacology 30:705-712, 2005.
BROWN, Z.W.; AMIT, Z.; AND ROCKMAN, G.E. Intraventricular self-administration of acetaldehyde, but not ethanol, in naïe laboratory rats. Psychopharmacology 64:271-276, 1979.
CORREA, M.; PASCUAL, M.; SANCHIS-S EGURA, C.; ET AL. Lead-induced catalase activity differentially modulates behaviors induced by short-chain alcohols. Pharmacology Biochemistry and Behavior 82:443-452, 2005.
DEITRICH, R.A. Acetaldehyde: Deja vu du jour. Journal of Studies on Alcohol 65:557-572, 2004.
ERIKSSON, C.J.P. The role of acetaldehyde in the actions of alcohol (update 2000). Alcoholism: Clinical and Experimental Research 25(Suppl. 5): 15S-32S, 2001.
ESCARABAJAL, D.; MIQUEL, M.; AND ARAGON, C.M.G. A psychopharmacological study of the relationship between brain catalase activity and ethanol-induced locomotor activity in mice. Journal of Studies on Alcohol 61:493-498, 2000.
FODDAI, M.; DOSIA, G.; SPIGA, S.; AND DIANA, M. Acetaldehyde increases dopaminergic neuronal activity in the VTA. Neuropsychopharmacology 29:530-536, 2004.
FREEMAN, T.L.; TUMA, D.J.; THIELE, G.M.; ET AL. Recent advances in alcohol-induced adduct formation. Alcoholism: Clinical and Experimental Research 29:1310-1316, 2005.
HE, X.X.; NEBERT, D.W.; VASILIOU, V.; ET AL. Genetic differences in alcohol drinking preference between inbred strains of mice. Pharmacogenetics 7:223-233, 1997.
ISSE, T.; OYAMA, T.; MATSUNO, K.; ET AL. Aldehyde dehydrogenase 2 activity affects symptoms produced by an intraperitoneal acetaldehyde injection, but not acetaldehyde lethality. Journal of Toxicological Sciences 30:315-328, 2005.
QUERTEMONT, E. Genetic polymorphism in ethanol metabolism: Acetaldehyde contribution to alcohol abuse and alcoholism. Molecular Psychiatry 9:570-581, 2004.
QUERTEMONT, E., AND TAMBOUR, S. Is ethanol a pro-drug? The role of acetaldehyde in the central effects of ethanol. Trends in Pharmacological Sciences 25:130-134, 2004.
QUERTEMONT, E.; TAMBOUR, S.; BERNAERTS, P.; ET AL. Behavioral characterization of acetaldehyde in C57BL/6J mice: Locomotor, hypnotic, anxiolytic and amnesic effects. Psychopharmacology 177:84-92, 2004.
QUERTEMONT, E.; TAMBOUR, S.; AND TIRELLI, E. The role of acetaldehyde in the neurobehavioral effects of ethanol: A comprehensive review of animal studies. Progress in Neurobiology 75:247-274, 2005.
RASKIN, N.H. Alcoholism or acetaldehydism? The New England Journal of Medicine 292:422-423, 1975.
RODD-HENRICKS, Z.A.; MELENDEZ, R.I.; ZAFFARONI, A.; ET AL. The reinforcing effects of acetaldehyde in the posterior ventral tegmental area of alcohol-preferring rats. Pharmacology Biochemistry and Behavior 72:55-64, 2002.
SMITH, B.R.; ARAGON, C.M.G.; AND AMIT, Z. Catalase and the production of brain acetaldehyde: A possible mediator of the psychopharmacological effects of ethanol. Addiction Biology 2:277-289, 1997.
TAMBOUR, S.; DIDONE, V.; TIRELLI, E.; AND QUERTEMONT, E. Dissociation between the locomotor and anxiolytic effects of acetaldehyde in the elevated plus-maze: Evidence that acetaldehyde is not involved in the anxiolytic effects of ethanol in mice. European Neuropsychopharmacology 15:655-662, 2005.
ZIMATKIN, S.M., AND DEITRICH, R.A. Ethanol metabolism in the brain. Addiction Biology 2:387-399, 1997.
ZIMATKIN, S.M., AND LINDROS, K.O. Distribution of catalase in rat brain: Aminergic neurons as possible targets for ethanol effects. Alcohol and Alcoholism 31:167-174, 1996.
ZIMATKIN, S.M.; PRONKO, S.P.; VASILIOU, V.; ET AL. Enzymatic mechanisms of ethanol oxidation in the brain. Alcoholism: Clinical and Experimental Research 30:1500-1505, 2006.