Behavioral and biochemical evidence of the role of acetaldehyde in the motivational effects of ethanol

Since Chevens’ report, in the early 50’s that his patients under treatment with the aldehyde 067
dehydrogenase inhibitor, antabuse, could experience beneficial effects when drinking 068
small volumes of alcoholic beverages, the role of acetaldehyde (ACD) in the effects of 069
ethanol has been thoroughly investigated on pre-clinical grounds. Thus, after more than 070
25 years of intense research, a large number of studies have been published on the 071
motivational properties of ACD itself as well as on the role that ethanol-derived ACD 072
plays in the effects of ethanol. Accordingly, in particular with respect to the motivational 073
properties of ethanol, these studies were developed following two main strategies: on 074
one hand, were aimed to challenge the suggestion that also ACD may exert motivational 075
properties on its own, while, on the other, with the aid of enzymatic manipulations or 076
077 have a role in ethanol motivational effects. Furthermore, recent evidence significantly 078
ACD inactivation, were aimed to test the hypothesis that ethanol-derived ACD might contributed to highlight, as possible mechanisms of action of ACD, its ability to commit 079
080 either dopaminergic and opioidergic transmission as well as to activate the Extracellular
signal Regulated Kinase cascade transduction pathway in reward-related brain structures. In conclusion, and despite the observation that ACD seems also to have inherited the elusive nature of its parent compound, the behavioral and biochemical evidence reviewed points to ACD as a neuroactive molecule able, on its own and as ethanol metabolite, to exert motivational effects.