Contribution of GABA(A) and GABA(B) receptors to the discriminative stimulus produced by gamma-hydroxybutyric acid.
The present study examined the involvement of GABA(A) and GABA(B) receptors in the discriminative stimulus effects of gamma-hydroxybutyric acid (GHB). Rats were trained to discriminate either 300 or 700 mg/kg GHB IG from water using a T-maze, food-reinforced drug-discrimination procedure. The direct GABA(B) agonist, baclofen, substituted completely for both training doses of GHB; its potency to substitute for GHB increased moderately as the training dose of GHB was increased. The positive GABA(A) modulator, diazepam, substituted partially for 300 mg/kg GHB, but failed to elicit GHB-appropriate responding in rats trained with the higher GHB dose. Finally, the GABA(B) antagonist, CGP 35348, completely blocked the discriminative stimulus effects of the high training dose of GHB, but only partially antagonized the effects of the low training dose. These results suggest that (a) GHB produces a compound stimulus, and (b) both GABA(B)- and GABA(A)-mediated cues are prominent components of this compound stimulus; the contribution of each component, however, appears to vary as the training dose of GHB is increased.
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Bernard B. Brodie Department of Neuroscience, Cagliari, Italy.
Agabio
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Reali
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Gessa
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Colombo
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D020155:3-Hydroxybutyric Acid / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D003463:Cues; D003975:Diazepam / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000187:drug effects*; D018080:Receptors, GABA-B / Q000187:drug effects*; D013268:Stimulation, Chemical
D018755:GABA Agonists; D018756:GABA Antagonists; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C066430:CGP 35348; D001418:Baclofen; D003975:Diazepam; D020155:3-Hydroxybutyric Acid