title: The H2O2 scavenger ebselen decreases ethanol-induced locomotor stimulation in mice.
abstract: BACKGROUND
  In the brain, the enzyme catalase by reacting with H(2)O(2) forms Compound I (catalase-H(2)O(2) system), which is the main system of central ethanol metabolism to acetaldehyde. Previous research has demonstrated that acetaldehyde derived from central-ethanol metabolism mediates some of the psychopharmacological effects produced by ethanol. Manipulations that modulate central catalase activity or sequester acetaldehyde after ethanol administration modify the stimulant effects induced by ethanol in mice. However, the role of H(2)O(2) in the behavioral effects caused by ethanol has not been clearly addressed. The present study investigated the effects of ebselen, an H(2)O(2) scavenger, on ethanol-induced locomotion.
  
  
  METHODS
  Swiss RjOrl mice were pre-treated with ebselen (0-50mg/kg) intraperitoneally (IP) prior to administration of ethanol (0-3.75g/kg; IP). In another experiment, animals were pre-treated with ebselen (0 or 25mg/kg; IP) before caffeine (15mg/kg; IP), amphetamine (2mg/kg; IP) or cocaine (10mg/kg; IP) administration. Following these treatments, animals were placed in an open field to measure their locomotor activity. Additionally, we evaluated the effect of ebselen on the H(2)O(2)-mediated inactivation of brain catalase activity by 3-amino-1,2,4-triazole (AT).
  
  
  RESULTS
  Ebselen selectively prevented ethanol-induced locomotor stimulation without altering the baseline activity or the locomotor stimulating effects caused by caffeine, amphetamine and cocaine. Ebselen reduced the ability of AT to inhibit brain catalase activity.
  
  
  CONCLUSIONS
  Taken together, these data suggest that a decline in H(2)O(2) levels might result in a reduction of the ethanol locomotor-stimulating effects, indicating a possible role for H(2)O(2) in some of the psychopharmacological effects produced by ethanol.
authors.affiliation: Àrea de Psicobiologia, Universitat Jaume I, Avda Sos Baynat, 12071 Castellón, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Ledesma
authors.forename: Laura
authors.initials: L
authors.lastname: Font
authors.forename: Carlos M G
authors.initials: CM
authors.lastname: Aragon
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D054833:Isoindoles; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction
chemical_list: D000975:Antioxidants; D001393:Azoles; D000697:Central Nervous System Stimulants; D054833:Isoindoles; D016566:Organoselenium Compounds; D002110:Caffeine; D000431:Ethanol; C042986:ebselen; D006861:Hydrogen Peroxide; D000661:Amphetamine; D002374:Catalase; D003042:Cocaine