Key role of acetaldehyde in the motivational properties of ethanol

Acetaldehyde is the first metabolite of ethanol. Since the early 50's, Chevens reported that his patients could experience beneficial effects when drinking small volumes of alcoholic drinks when under treatment with antabuse. In line with a potential positive reinforcing effect of acetaldehyde, more recently it was reported that acetaldehyde stimulates dopaminergic neuronal activity and this yields an increment in dopamine microdialysate in the Nucleus Accumbens possibly by a local action on Ih and IA. We have further shown that by blocking the metabolism of ethanol to acetaldehyde and/or sequestering acetaldehyde reduces ethanol- and acetaldehyde-induced conditioned place preference. Further experiments have shown that animals rapidly acquire, maintain and, after an extinction period, reinstate self-administration behaviour for acetaldehyde. Interestingly, acetaldehyde and ethanol reached similar break-point values, an index of animals’ motivation to work for reinforcers. In summary, the gathered evidence suggests that acetaldehyde plays a critical role in the psychopharmacological effects of ethanol, bearing potential relevance for the development of pharmacological treatments of alcohol abuse and alcoholism.