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


OBJECTIVE
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.
Goodwin
Amy K
AK
Johns Hopkins Bayview, Behavioral Biology Research Center, 5510 Nathan Shock Dr., Suite 3000, Baltimore, MD 21224, USA.
Froestl
Wolfgang
W
Weerts
Elise M
EM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001567:Benzocycloheptenes / Q000494:pharmacology; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010215:Papio; D018080:Receptors, GABA-B / Q000502:physiology*; D012978:Sodium Oxybate / Q000494:pharmacology*
D001567:Benzocycloheptenes; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; C066471:NCS 382; C079148:(3-aminopropyl)(n-butyl)phosphinic acid; D012978:Sodium Oxybate
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