Opioid antagonists block acetaldehyde-induced increments in dopamine neurons activity

Background: Acetaldehyde is the main metabolite of ethanol ingested through alcoholic beverages. Traditionally considered aversive is presently being viewed as an activating agent of the mesolimbic dopamine system but underlying mechanisms are only partially known. Methods: Through in vivo electrophysiology experiments in rats we have studied the role of endogenous opioids in acetaldehyde-induced increments in dopamine activity. Results: Here we show that acetaldehyde-induced increase in firing rate, burst firing and spikes/burst of antidromically-identified ventro-tegmental area nucleus accumbens-projecting neurons are abolished by pretreatment with the opiate unselective antagonist naltrexone (0.4 mg/kg/ip). Similar effects are obtained after administration of naloxone (0.1 mg/kg/iv). These results indicate that endogenous opiate system(s) participate in acetaldehyde-induced increments in dopaminergic neuronal activity. Conclusion: These data may explain the reduction in acetaldehyde-induced dopamine release in the nucleus accumbens after blockade of opiate receptors. Considering the paucity of efficacious therapies in alcoholism, and recent developments in ethanol-derived acetaldehyde effects, further experiments are warranted to further elucidate its role as a biomarker potentially useful to develop new strategies in the search for effective compounds aimed at reducing excessive alcohol intake, abuse and ultimately alcoholism.