Rationale: Hydrogen peroxide (H sub(2)O sub(2)) 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 H sub(2)O sub(2) 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 H sub(2)O sub(2) levels. Results: LA selectively blocked the acquisition of ethanol-induced CPP. Moreover, this compound impaired the reconditioning of ethanol-induced CPP. Additionally, we found that LA diminished H sub(2)O sub(2) levels in the brain. Conclusions: These data suggest that a decline in H sub(2)O sub(2) 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.