Alpha-lipoic acid, a scavenging agent for H2O2, reduces ethanol-stimulated locomotion in mice

Abstract

Rationale The main system of central ethanol oxidation is mediated by the enzyme catalase. By reacting with H2O2, brain catalase forms compound I (the catalase–H2O2 system), which is able to oxidize ethanol to acetaldehyde in the brain. Previous studies have demonstrated that pharmacological manipulations of brain catalase activity modulate the stimulant effects of ethanol in mice. However, the role of H2O2 in the behavioral effects of ethanol has not yet been clearly addressed. Objectives In the present study, we investigated the effects of alpha-lipoic acid (LA), a scavenging agent for H2O2, on ethanol-induced locomotor stimulation. Methods CD-1 mice were pretreated with LA [0–100 mg/kg, intraperitoneally (IP)] 0–60 min prior to administration of ethanol (0–3.75 g/kg, IP). In another experiment, animals were pretreated with LA (0, 25, or 50 mg/kg, IP) 30 min before cocaine (10 mg/kg, IP), amphetamine (2 mg/kg, IP), or caffeine (25 mg/kg, IP). After these treatments the animals were placed in an open-field chamber and their locomotor activity was measured for 20 min. Results LA 25, 50, and 100 mg/kg IP prevented ethanol-induced locomotor stimulation. LA did not affect the locomotor-stimulating effects of cocaine, amphetamine, and caffeine. Additionally, we demonstrated that LA prevents the inactivation of brain catalase by 3-amino-1,2,4-triazole, thus indicating that H2O2 levels are reduced by LA. Conclusions These data support the idea that a decrease in cerebral H2O2 production by LA administration inhibits ethanol-stimulated locomotion. This study suggests that the brain catalase–H2O2 system, and by implication centrally formed acetaldehyde, plays a key role in the psychopharmacological effects of ethanol.