The discriminative stimulus effects of diazepam in rats at two training doses.
Two groups of rats were trained to discriminate either a low (1 mg/kg) or a high (10 mg/kg) intraperitoneal dose of diazepam from vehicle injections in a two-lever, food-reinforcement procedure. Comparison of the dose-response curves demonstrated a difference in the intensity of the stimulus effects. A number of benzodiazepine agonists and partial agonists were tested for stimulus generalization. The stimulus effect in both groups of rats generalized fully to triazolam, alprazolam, adinazolam and pentobarbital. Ro 17-1812 occasioned nearly full generalization in both groups of rats with a shallow dose-response slope. The low-, but not the high-dose stimulus effect generalized to the following compounds: CL 218872, ZK 91296 (ethyl-5-benzyloxy-4-methoxymethyl-B-carboline-3-carboxylate), CGS 20625 (2-(4-methoxyphenyl)-2,3,5,6,7,8,9,10-octahydrocyclohepta(b)pyrazo lo(3,4- d)pyridin-3-one) and U-78875 (3-(5-cyclo-propyl-1,2,4-oxadiazol-3-yl)-5-(1- methylethyl)imidazol(1,5-a)quinoxalin-4(5H)-o-ne). Flumazenil, FD-7142 (N-methyl-beta-carboline-3-carboxamide), buspirone and morphine occasioned predominantly vehicle-appropriate responses in both groups of rats. In the low-dose group, pretreatment with flumazenil (10 mg/kg) reduced responding on the diazepam-lever for the following compounds: diazepam, Ro 17-1812 (cyclopropylmethyl-(S)-8-chloro-12,12a-dihydro- 9-oxo-9H,11H-aceto(2,1-C)imidazo(1,5-a)(1,4)benzo-diazepine-1-carboxylat e), ZK 91296, CGS 20625, CL 218872 and U-78875.(ABSTRACT TRUNCATED AT 250 WORDS)
Central Nervous System Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
A H
AH
Tang
S R
SR
Franklin
D000525:Alprazolam / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002065:Buspirone / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014229:Triazolam / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D002243:Carbolines; D011720:Pyrazoles; D011724:Pyridazines; C054732:CGS 20625; D001569:Benzodiazepines; D014229:Triazolam; D005442:Flumazenil; C035874:FG 7142; C021604:CL 218872; D009020:Morphine; C038933:ZK 91296; C049715:Ro 17-1812; D010424:Pentobarbital; C039668:adinazolam; D003975:Diazepam; D002065:Buspirone; D000525:Alprazolam