Role of acetaldehyde in the actions of ethanol on the brain--a review

Over the last 30 years, acetaldehyde has been postulated to mediate various actions of ethanol on the brain. Experiments have studied ethanol consumption after acetaldehyde infusions into the brain, in rodents with high or low activities of hepatic and brain ethanol-metabolizing enzymes, and after treatment with drugs that alter the metabolism of acetaldehyde after ethanol ingestion. Evidence that acetaldehyde is involved in the actions of ethanol has been inconsistent because of the lack of knowledge of the brain acetaldehyde concentrations required to exert their effects, the lack of correlation between the activities of ethanol-metabolizing enzymes across strains of rodents and ethanol consumption, and the lack of specificity of drugs altering acetaldehyde metabolism. The formation of significant amounts of acetaldehyde the brain in vivo after ethanol ingestion and by what mechanism has not been clearly established, although catalase is a promising candidate. Future research needs to directly demonstrate in brain the formation of acetaldehyde in vivo, determine the concentrations in brain areas involved in ethanol consumption, and evaluate the possible actions of drugs other than an ability to block acetaldehyde metabolism.