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.