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

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摘要：

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 (32–420mg/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 (10–56mg/kg), the putative GHB antagonist NCS-382 (0.1–10mg/kg), or vehicle were administered alone and then in combination with GHB (320mg/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.

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关键词：

Xyrem Reinforcement schedule Operant behavior Conditioned performance Feeding Ataxia

DOI：

10.1007/s00213-005-2165-y

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年份：

2005