Discriminative stimulus effects of diazepam in rats: evidence for a maximal effect.
Rats were trained to discriminate between saline and either 0.3, 1.0, 3.0 or 6.0 mg/kg of diazepam in a two-choice, discrete-trial avoidance procedure. Diazepam, chlordiazepoxide, flurazepam and pentobarbital occasioned dose-related increases in diazepam-appropriate responding in all four training dose groups. Increasing the training dose of diazepam from 0.3 to 1.0 mg/kg resulted in approximately a 3-fold shift to the right in the dose-effect curves for each of these four drugs. However, increasing the training dose to 3.0 or 6.0 mg/kg did not result in additional, concomitant shifts in these dose-effect curves. Moreover, the dose-effect curves of nine additional benzodiazepine analogs also did not differ markedly in rats trained with either 1.0 or 3.0 mg/kg of diazepam. The nonbenzodiazepines ethanol, phencyclidine, cyproheptadine and ketocyclazocine failed to produce diazepam-like discriminative stimuli in rats trained with either 0.3, 1.0 or 3.0 mg/kg of diazepam. In rats trained with 1.0 mg/kg of diazepam, Ro 11-6896, but not its inactive stereoisomer Ro 11-6893, occasioned diazepam-appropriate responding. Furthermore, the selective benzodiazepine antagonist CGS8216 blocked the effects of diazepam but not the diazepam-like effects of pentobarbital. These results demonstrate that the discriminative effects of diazepam are qualitatively similar across this 20-fold range of training doses; quantitatively, the discriminative effects of diazepam appear to reach a maximum and plateau above a training dose of 1.0 mg/kg in rats.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000037:antagonists & inhibitors; D002707:Chlordiazepoxide / Q000494:pharmacology; D003533:Cyproheptadine / Q000494:pharmacology; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats
D014151:Anti-Anxiety Agents; D011720:Pyrazoles; D001569:Benzodiazepines; D003533:Cyproheptadine; D000431:Ethanol; D002707:Chlordiazepoxide; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; D010424:Pentobarbital; D010622:Phencyclidine; D003975:Diazepam