Brain metabolism of ethanol and alcoholism: an update

It has long been suggested that some of the neuropharmacological, neurochemical and behavioural effects of ethanol are mediated by its first metabolite, acetaldehyde. In spite of the well documented psychoactivity of acetaldehyde, the precise role of this compound in alcohol abuse remains a matter of intense debate among scientists devoted to the study of alcoholism. Very frequently, the main drawback has been related to the presence of adequate levels of acetaldehyde or its derivatives inside the brain after ethanol ingestion. Since penetration into the central nervous system from blood of peripherically derived acetaldehyde is very low due to the high aldehyde dehydrogenase activity at the blood-brain barrier, several authors called into question the acetaldehyde implication in the toxicity and neurobehavioral effects of ethanol. The confirmation in several laboratories of the existence of enzymatic mechanisms of ethanol oxidation in the brain has revitalized the old theories supporting the acetaldehyde contribution to alcohol abuse and alcoholism. In this paper, we review current data on the brain metabolism of ethanol. We focused on the description of the enzymatic mechanisms involved in this metabolic process, reviewing the constitutive expression, catalytic activity and inhibition and inducibility of the enzymes involved in brain ethanol metabolism. We also analyze old and recent data on their regional distribution and cellular localization in the central nervous system, with special reference to the mesocorticolimbic system, a dopaminergic brain pathway that plays an important role in drug and ethanol reinforcement.