Midazolam cue in rats: effects of Ro 15-1788 and picrotoxin.
The discriminative stimulus effect of midazolam, a short-acting benzodiazepine, was used for testing the effects of drugs thought to act as antagonists at different sites in the proposed benzodiazepine receptor complex. Rats were trained in a standard two-bar operant conditioning procedure with food reinforcers delivered on a tandem schedule. The 0.4 mg/kg dose of midazolam used for training was well discriminated, typically yielding at least 95% correct responding. The benzodiazepine receptor antagonist Ro 15-1788 blocked the discriminative effect of midazolam but did not influence generalization to pentobarbitone (7.5 mg/kg). The indirect GABA antagonist picrotoxin attenuated both generalization to pentobarbitone and its response rate-reducing effect. Picrotoxin had no effect on the discriminative effect of midazolam at 0.4 mg/kg but it blocked the effect of 0.1 mg/kg. Even in doses which reduced overall response rates, nicotine did not block discrimination of midazolam (0.4 mg/kg). The results are consistent with models which postulate a GABA-linked ion channel which is a site of action for barbiturates and which is "downstream" of the benzodiazepine receptor itself.
D000818:Animals; D001569:Benzodiazepines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil; D008297:Male; D008874:Midazolam; D009538:Nicotine / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D001569:Benzodiazepines; D001570:Benzodiazepinones; D005442:Flumazenil; D008874:Midazolam; D009538:Nicotine; D010424:Pentobarbital; D010852:Picrotoxin; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid