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

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.

• Authors: Amy K Goodwin, Wolfgang Froestl, Elise M Weerts
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 180 Issue 2 Pg. 342-51 (Jul 2005) ISSN: 0033-3158 [Print] Germany
• PMID: 15739078 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benzocycloheptenes
• Organophosphorus Compounds
• Receptors, GABA-B
• NCS 382
• (3-aminopropyl)(n-butyl)phosphinic acid
• Sodium Oxybate

Topics

• Animals
• Behavior, Animal (drug effects)
• Benzocycloheptenes (pharmacology)
• Male
• Organophosphorus Compounds (pharmacology)
• Papio
• Receptors, GABA-B (physiology)
• Sodium Oxybate (pharmacology)