MUSCIMOL-LIKE DISCRIMINATIVE STIMULUS EFFECTS OF GABA AGONISTS IN RATS

The discriminative stimulus effects of GABAergic drugs were evaluated in rats trained to discriminate the direct GABA, agonist, muscimol (1. 0 mg/kg IP), from saline under a two-lever fixed ratio (FR) 32 schedul e of food reinforcement. Another direct GABA(A) agonist, THIP, produce d full substitution for muscimol, however, at doses producing response rate decreasing effects. Diazepam, an allosteric modulator of GABA-me diated Postsynaptic inhibition, yielded a maximum of 50% muscimol-leve r responding at a dose that also decreased rates of responding. Partia l substitution for muscimol (maximal levels of 71% muscimol-lever resp onding) was also produced by the GABA agonist progabide. Propofol, an anesthetic that potentiates GABA(A) receptor function, and the GABA up take inhibitor, tiagabine, produced no greater than 53 and 48% muscimo l-lever responding, respectively. Valproic acid, a reversible GABA tra nsaminase inhibitor, failed to substitute for muscimol, and vigabatrin , an irreversible GABA transaminase inhibitor, yielded a maximal 46% m uscimol-lever responding. These results demonstrate the pharmacologica l specificity of muscimol discrimination by showing that only direct a gonists for the GABA site on the GABA(A) receptor complex produce full substitution. GABA agonists acting by other mechanisms can be disting uished from muscimol and THIP in this procedure. (C) 1998 Elsevier Sci ence Inc.