Attenuation of cocaine-seeking by GABA B receptor agonists baclofen and CGP44532 but not the GABA reuptake inhibitor tiagabine in baboons.
The current study evaluated the effects of drugs that increase GABA levels by activation of GABA(B) receptors (baclofen and CGP44532) or by inhibition of GABA reuptake (tiagabine) on the reinstatement of extinguished lever responding produced by priming doses of cocaine in baboons (i.e., cocaine-seeking). Cocaine self-injection was established and maintained under a fixed ratio (FR10) schedule of reinforcement during daily 2h sessions. Lever responding was extinguished by substituting vehicle (saline) for cocaine until the number of self-injections decreased to 10 or less per session for two consecutive sessions (defined as extinction). Once extinction occurred, priming doses of cocaine (0.1-3.2mg/kg, i.v.) were administered during extinction conditions. Administration of priming doses of cocaine significantly increased cocaine-seeking in a dose-dependent manner. Cocaine-seeking produced by priming doses of cocaine were attenuated by pretreatment with baclofen (N=5) or CGP44532 (N=5) but not tiagabine (N=3). The doses of baclofen (0.32 mg/kg), and CGP445532 (0.32 mg/kg) that reduced cocaine-seeking produced by cocaine priming doses did not reinstate cocaine-seeking and did not produce overt effects when administered alone. These data indicate that GABA(B) agonists may reduce relapse to cocaine taking.
Weerts
Elise M
EM
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University, Bayview Behavioral Biology Research Center, 5510 Nathan Shock Drive, Baltimore, MD 21224, USA. eweerts@jhmi.edu
Froestl
Wolfgang
W
Kaminski
Barbara J
BJ
Griffiths
Roland R
RR
D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects; D001418:Baclofen / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000523:psychology*; D018756:GABA Antagonists / Q000494:pharmacology*; D058786:GABA-B Receptor Agonists; D008297:Male; D009042:Motivation; D009557:Nipecotic Acids / Q000494:pharmacology*; D063065:Organophosphonates / Q000494:pharmacology*; D048530:Papio anubis; D010721:Phosphinic Acids; D012646:Self Administration; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*
C112036:3-amino-2-(S)-hydroxypropyl-methyl-phosphinic acid; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D009557:Nipecotic Acids; D063065:Organophosphonates; D010721:Phosphinic Acids; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D000078308:Tiagabine