Attenuation of cocaine-seeking by GABAB receptor agonists baclofen and CGP44532 but not the GABA reuptake inhibitor tiagabine in baboons

Research output: Contribution to journalArticle

Abstract

The current study evaluated the effects of drugs that increase GABA levels by activation of GABAB 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 2 h 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 (0.1-3.2 mg/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 GABAB agonists may reduce relapse to cocaine taking.

Original languageEnglish (US)
Pages (from-to)206-213
Number of pages8
JournalDrug and alcohol dependence
Volume89
Issue number2-3
DOIs
StatePublished - Jul 10 2007

Keywords

  • GABA receptor agonist
  • Primates
  • Reinforcement
  • Reinstatement
  • Relapse
  • Self-administration

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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