Involvement of gamma-hydroxybutyrate (GHB) and GABA-B receptors in the acute behavioral effects of GHB in baboons

Amy K. Goodwin, Wolfgang Froestl, Elise M. Weerts

Research output: Contribution to journalArticle

Abstract

Rationale: Gamma-hydroxybutyrate (GHB) is used for the treatment of narcolepsy, but it is also a drug of abuse. The behavioral pharmacology of GHB is not well defined. Objectives: The current study was conducted to characterize the behavioral effects of a range of GHB doses in baboons (N=4) and to evaluate whether a GABA-B receptor antagonist and a GHB receptor antagonist would block a behaviorally active dose of GHB. Methods: In the first experiment, GHB (32-420 mg/kg) or vehicle was administered via an intragastric catheter. Sixty min after dosing, subjects were presented with a fine-motor task and observed. Food pellets were available under a fixed-ratio schedule of reinforcement 20-h/day. In the second experiment, the GABA-B antagonist CGP36742 (10-56 mg/kg), the putative GHB antagonist NCS-382 (0.1-10 mg/kg), or vehicle were administered alone and then in combination with GHB (320 mg/kg). Results: GHB dose-dependently decreased the number of food pellets earned. Performance in the motor task was also impaired and accompanied by signs of sedation and gastrointestinal discomfort. Pretreatment with CGP36742 antagonized GHB-induced suppression of food-maintained behavior and performance on the fine-motor task. Signs of abdominal discomfort, ataxia, and muscle relaxation produced by GHB were also reduced by pretreatment with CGP36742. In contrast, pretreatment with NCS-382 sometimes restored performance in the fine-motor task and increased food-maintained behavior, but the effect was variable across doses and baboons. Some doses of NCS-382 appeared to exacerbate ataxia and gastrointestinal discomfort produced by GHB in some subjects. Conclusions: These data indicate that while GABA-B receptors play a significant role in mediating the behavioral effects of GHB in baboon, the role of GHB receptors is less clear.

Original languageEnglish (US)
Pages (from-to)342-351
Number of pages10
JournalPsychopharmacology
Volume180
Issue number2
DOIs
StatePublished - Jul 1 2005

Keywords

  • Ataxia
  • Conditioned performance
  • Feeding
  • Operant behavior
  • Reinforcement schedule
  • Xyrem

ASJC Scopus subject areas

  • Pharmacology

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