Alpha-Lipoic Acid Reduces Ethanol Self-Administration in Rats

Abstract

The main system of central ethanol (EtOH) oxidation is mediated by the enzyme catalase. By reacting with H2 O2 , brain catalase forms compound I (the catalase-H2 O2 system), which is able to oxidize EtOH to acetaldehyde (ACD) in the brain. We have previously shown that ACD regulates EtOH motivational properties and possesses reinforcing effects by itself. In this study, we investigate the effects of alpha-lipoic acid (ALA), a scavenging agent for H2 O2 , on oral EtOH self-administration. To this end, we trained Wistar rats to orally self-administer EtOH (10%) by nose poking. The effect of intraperitoneal pretreatment with ALA was evaluated during (i) maintenance of EtOH self-administration, (ii) EtOH self-administration under a progressive ratio (PR) schedule of reinforcement, and (iii) oral EtOH priming to induce reinstatement of EtOH seeking behavior. Moreover, we tested the effect of ALA on saccharin (0.05%) reinforcement, as assessed by oral self-administration. The results indicate that ALA dose-dependently reduced the maintenance, the break point of EtOH self-administration under a PR and the reinstatement of EtOH seeking behavior without suppressing saccharin self-administration. These results support that ALA may have a potential use in alcoholism treatment.