Attenuation of d-amphetamine self-administration by baclofen in the rat: behavioral and neurochemical correlates.
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.
Brebner
Karen
K
Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 2A1, Canada. brebner@interchange.ubc.ca
Ahn
Soyon
S
Phillips
Anthony G
AG
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
D000697:Central Nervous System Stimulants; D018755:GABA Agonists; D001418:Baclofen; D003913:Dextroamphetamine; D004298:Dopamine