title: Attenuation of d-amphetamine self-administration by baclofen in the rat: behavioral and neurochemical correlates.
abstract: BACKGROUND
  Recent reports have demonstrated that gamma-aminobutyric acid (GABA)-ergic compounds attenuate the reinforcing effects of cocaine in rats. Baclofen, a GABA(B) receptor agonist, appears to be particularly effective in this respect, suggesting that GABA(B) receptor activation is critically involved in mediating anti-cocaine effects. Amphetamine, like cocaine, is a psychomotor stimulant with high abuse potential in humans.
  
  
  OBJECTIVE
  The purpose of the present investigation was to determine whether baclofen may attenuate the reinforcing effects of d-amphetamine (dAMPH) in rats. Dose-response curves were generated to examine the effect of three doses of baclofen (1.8, 3.2 or 5.6 mg/kg, IP) on dAMPH intravenous self-administration (IVSA). Separate groups were trained to self-administer two doses of dAMPH (0.1 mg/kg or 0.2 mg/kg per injection) under either a fixed-ratio (FR) or progressive ratio (PR) schedule of reinforcement. Microdialysis was performed in an additional group of rats to examine the effect of baclofen on dAMPH-induced increases in dopamine (DA) efflux in the nucleus accumbens (NAc).
  
  
  RESULTS
  Pretreatment with baclofen produced dose-dependent reductions in responding for dAMPH under both the FR and PR schedules, and attenuated dAMPH-induced increases in DA levels in the NAc.
  
  
  CONCLUSIONS
  These results add to previous findings showing that baclofen attenuates the reinforcing effects of psychostimulant drugs, and suggest that further investigation into the effects of GABA(B) receptor agonists on drug self-administration is warranted.
authors.affiliation: Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 2A1, Canada. brebner@interchange.ubc.ca
authors.forename: Karen
authors.initials: K
authors.lastname: Brebner
authors.forename: Soyon
authors.initials: S
authors.lastname: Ahn
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Phillips
mesh_terms: D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D000818:Animals; D001418:Baclofen / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D003216:Conditioning, Operant / Q000187:drug effects; D003913:Dextroamphetamine / Q000493:pharmacokinetics; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000627:therapeutic use*; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012646:Self Administration; D015819:Substance Abuse, Intravenous
chemical_list: D000697:Central Nervous System Stimulants; D018755:GABA Agonists; D001418:Baclofen; D003913:Dextroamphetamine; D004298:Dopamine