GABAergic modulation of the discriminative stimulus effects of methamphetamine

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To assess whether γ-aminobutyric acid (GABA) modulation of dopamine is important in mediation of the discriminative stimulus effects of methamphetamine, the GABA compounds chlordiazepoxide (benzodiazepine site agonist), pentobarbital (barbiturate site agonist), bicuculline and pentylenetetrazol (GABAA receptor antagonists) were tested in Sprague-Dawley rats trained to discriminate methamphetamine (1 mg/kg, i.p.) from saline. Each of the compounds produced modest amounts of methamphetamine- appropriate responding (20-35%) when tested alone. When tested in combination with methamphetamine, the antagonists (bicuculline and pentylenetetrazol) failed to shift the methamphetamine dose-effect curve. In contrast, chlordiazepoxide (25 mg/kg, i.p.) reduced methamphetamine-appropriate responding at each dose of methamphetamine tested, and pentobarbital (10 mg/kg, i.p.) dose-dependently decreased the discriminative stimulus effects of 1 mg/kg methamphetamine. In conclusion, GABAA antagonists and positive modulators likely do not produce methamphetamine-like stimulus effects. However, activation of GABA A receptors can interfere with the discriminative stimulus effects of methamphetamine.

Original languageEnglish
Pages (from-to)261-266
Number of pages6
JournalBehavioural pharmacology
Issue number4
StatePublished - Jul 2005


  • Drug discrimination
  • GABA receptor
  • Methamphetamine
  • Rat


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