Ruolo dell’acetaldeide nelle proprietà motivazionali dell’etanolo: studio di Self-administration orale nel ratto

Our line of research was focused on the study of the motivational and rewarding properties of ethanol. Particularly, our research activity examined the role of acetaldehyde, in mediating the reinforcing properties of ethanol. We show that acetaldehyde is orally self-administered by Wistar rats and possesses its own motivational and reinforcing effects. Interestingly, we have observed that acetaldehyde reinforcing effects are reduced by L-Cysteine, a not essential amino acid, which was previously shown to reduce ethanol self-administration. Furthermore, acetaldehyde selfadministration was reduced by the pre-treatment with the nonselective opioid receptor antagonist, naltrexone, and with the μ1-selective opioid receptor antagonist, naloxonazine. This suggests an involvement of the endogenous opioid system in the central actions of acetaldehyde as an ethanol metabolite. In order to further our understanding on the role of centrally formed acetaldehyde in the mechanism of action of alcoholic beverages, we studied the role of catalase, the main enzymatic system that oxidizes ethanol to acetaldehyde in the central nervous system. In this phase we studied the effect of alpha-lipoic acid, an antioxidant agent which is able to reduce H2O2 concentrations in the brain, on ethanol oral self-administration. These experiments show that alpha-lipoic acid intraperitoneal administration reduced all self-administration phases in a dose-dependent manner. These studies underscore the role of acetaldehyde in the motivational properties of ethanol and suggest that acetaldehyde may be a pharmacological “target” for devising new therapeutic strategies in alcoholism.