Role of acetaldehyde in alcohol addiction : current evidence and future perspectives

The effects of alcohol have been widely studied during the past century, corroborating the idea that this tiny chemical compound acts throughout most of our neurotransmitter systems since it is capable of inducing addictive behaviour. Two of the most serious problems of alcohol addiction are craving and relapse; several studies have demonstrated that relapse is related to the anxious state which occurs during withdrawal, and it has been proved that this behavioural modifications results from an alteration of the dopaminergic and serotonergic systems. An important role in the neurobiology of alcohol addiction is played by acetaldehyde (ACD), ethanol first metabolite. Our recent studies indeed, have demonstrated that ACD itself is able to induce CRH release from hypothalamic explants, underlying the central role played by ACD in alcohol-induced modifications of the HPA axis. Moreover, for the first time, this group has shown that ACD is able to induce and maintain an operant drinking behaviour after repeated abstinence periods, and in the presence of a conflict situation in rats, mimicking the same characteristics as alcohol. ACD is produced either peripherally or within the brain by alcohol dehydrogenase and catalase, respectively. Studies assert that the highest concentrations of catalase in the brain are mainly located in aminergic neurons suggesting that ACD could take part in alcohol action in those circuitries. Further investigations are then necessary to fully understand the molecular mechanisms underlying the neurochemical and behavioural modifications induced by ACD, as a mediator of alcohol activity in the brain.peer-reviewe