Acquisition and reconditioning of ethanol-induced conditioned place preference in mice is blocked by the H2O2 scavenger alpha lipoic acid

Abstract

Rationale Hydrogen peroxide (H2 O2) is the co-substrate used by catalase to metabolize ethanol to acetaldehyde in the brain. This centrally formed acetaldehyde has been involved in several ethanol-related behaviors. Objectives The present research evaluated the effect of the H2 O2 scavenger, alpha lipoic acid (LA), on the acquisition and reconditioning of ethanol-induced conditioned place preference (CPP). Methods Mice received pairings of a distinctive floor stimulus (CS+) associated with intraperitoneal injections of ethanol (2.5 g/kg). On alternate days, animals received pairings of a different floor stimulus (CS−) associated with saline injections. A different group of animals received pairings with the (CS−) associated with saline injections, and on alternate days they received LA (100 mg/kg) injected 30 min prior to ethanol (2.5 g/kg) administration paired with the (CS+). A preference test assessed the effect of LA on the acquisition of ethanol-induced CPP. A similar procedure was followed to study the effect of LA on the acquisition of cocaine- and morphine-induced CPP. A separate experiment evaluated the effect of LA on the reconditioning of ethanol-induced CPP. In addition, we investigated the consequence of LA administration on central H2 O2 levels. Results LA selectively blocked the acquisition of ethanolinduced CPP. Moreover, this compound impaired the reconditioning of ethanol-induced CPP. Additionally, we found that LA diminished H2 O2 levels in the brain. Conclusions These data suggest that a decline in H2 O2 availability by LA might impede the formation of brain ethanol-derived acetaldehyde by catalase, which results in an impairment of the rewarding properties of ethanol.