Effects of GABAA compounds on mCPP drug discrimination in rats

Michael B. Gatch, Eunsun Jung, Cleatus J. Wallis, Harbans Lal

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Male Long-Evans rats were trained to discriminate mCPP (1.4 mg/kg, i.p.) from saline, using a two-lever, food-reinforced operant task. The GABAA antagonist, bicuculline (0.16-0.64 mg/kg), partially substituted for mCPP, whereas the benzodiazepine antagonist, flumazenil (1-10 mg/kg), and the benzodiazepine inverse agonist, Ro 15-4513 (0.25-2.5 mg/kg), failed to substitute for mCPP. Bicuculline produced no change in response rate, whereas Ro 15-4513 dose-dependently decreased responding. Flumazenil produced a small increase in response rates. Flumazenil (10 mg/kg), Ro 15-4513 (1.25 mg/kg), and the benzodiazepine agonists alprazolam (0.64 mg/kg) and diazepam (5 mg/kg) full agonist all failed to block the mCPP discriminative stimulus. When given in combination with mCPP, Ro 15-4513 and alprazolam both produced lower response rates than did mCPP alone, whereas flumazenil and diazepam did not significantly alter response rates. These findings provide evidence that GABAA antagonists modulate the discriminative stimulus effects of mCPP, but that these effects are not mediated by activity at the benzodiazepine site.

Original languageEnglish
Pages (from-to)2657-2665
Number of pages9
JournalLife Sciences
Volume71
Issue number22
DOIs
StatePublished - 18 Oct 2002

Keywords

  • 5-HT (5-hydroxytryptamine, serotonin)
  • Drug discrimination
  • GABA receptor
  • Rat
  • mCPP (1-(3-chlorophenyl)-piperazine)

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