title: α-Lipoic acid, a scavenging agent for H₂O₂, reduces ethanol-stimulated locomotion in mice.
abstract: BACKGROUND
  The main system of central ethanol oxidation is mediated by the enzyme catalase. By reacting with H(2)O(2), brain catalase forms compound I (the catalase-H(2)O(2) 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 H(2)O(2) in the behavioral effects of ethanol has not yet been clearly addressed.
  
  
  OBJECTIVE
  In the present study, we investigated the effects of alpha-lipoic acid (LA), a scavenging agent for H(2)O(2), 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 H(2)O(2) levels are reduced by LA.
  
  
  CONCLUSIONS
  These data support the idea that a decrease in cerebral H(2)O(2) production by LA administration inhibits ethanol-stimulated locomotion. This study suggests that the brain catalase-H(2)O(2) system, and by implication centrally formed acetaldehyde, plays a key role in the psychopharmacological effects of ethanol.
authors.affiliation: Area de Psicobiologia, Universitat Jaume I, Avda. Sos Baynat s/n, 12071 Castellón de la Plana, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Ledesma
authors.forename: Carlos M G
authors.initials: CM
authors.lastname: Aragon
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D016166:Free Radical Scavengers; D000431:Ethanol; D008063:Thioctic Acid; D006861:Hydrogen Peroxide