The discriminative stimulus effects of diazepam in rats at two training doses

AH Tang and SR Franklin

Central Nervous System Diseases Research, Upjohn Company, Kalamazoo, MI 49001.

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)

Volume 258, Issue 3, pp. 926-931, 09/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics

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