Discriminative stimulus properties of CGS 9896: interactions within the GABA/benzodiazepine receptor complex.
Male rats were trained to discriminate the stimulus effects of CGS 9896 (30.0 mg/kg) from its vehicle. Once trained, discriminative performance was observed to be dose-responsive in the 3.75-30.0 mg/kg range and analysis of the dose-response curve generated an ED50 of 6.44 mg/kg. Generalization testing with chlordiazepoxide and pentobarbital produced CGS 9896-appropriate responding, whereas administration of the GABA agonists SL 75 102 resulted in 75% (intermediate) generalization to the CGS 9896 discriminative stimulus. Although full antagonism of the CGS 9896 cue was obtained following administration of Ro15-1788 and pentylenetetrazole, the inverse agonist DMCM failed to provide complete antagonism. These results suggest that the discriminative properties of CGS 9896 are consistent with its activity as a benzodiazepine receptor agonist.
Leidenheimer
N J
NJ
Department of Pharmacology, Northeastern Ohio Universities, College of Medicine, Rootstown 44272.
Schechter
M D
MD
D000818:Animals; D002243:Carbolines / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D011720:Pyrazoles / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D002243:Carbolines; D011720:Pyrazoles; D011963:Receptors, GABA-A; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D002707:Chlordiazepoxide; C017984:progabide acid; C034704:2-(4-chlorophenyl)-2,5-dihydropyrazolo(4,3-c)quinoline-3(3H)-one; D010424:Pentobarbital; D010433:Pentylenetetrazole