Differential interactions between chlordiazepoxide, pentobarbital and benzodiazepine antagonists Ro 15-1788 and CGS 8216 in a drug discrimination procedure.
Rats were trained to discriminate either chlordiazepoxide (CDP, 4 mg/kg, IP, N = 8) or pentobarbital (PB, 10 mg/kg, IP, N = 8) from saline in a two-lever food-reinforced procedure. CDP and PB dose-dependently substituted for each other (greater than or equal to 90% drug lever responses); indicating that their discriminative stimulus properties were closely similar. However, discriminative stimulus control induced by CDP and PB differentially was affected by the proposed benzodiazepine (BDZ) antagonists Ro 15-1788 (0.08-20 mg/kg, IP) and CGS 8216 (2.5-20 mg/kg, IP) in each experimental group; suggesting that the discriminative stimulus properties of CDP and PB are mediated by different mechanisms of action. When administered alone, Ro 15-1788 (5 and 20 mg/kg), but not CGS 8216, induced CDP like discriminative effects, suggesting that Ro 15-1788 may have partial (BDZ like) agonist properties, not shown by CGS 8216. Additional evidence for a behavioral difference between Ro 15-1788 and CGS 8216 is suggested by differential effects of both compounds on response rate. The results may reflect differential interactions of the compounds with the BDZ receptor-GABA receptor-Cl- ionophore complex.
D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage*; D002707:Chlordiazepoxide / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004193:Discrimination Learning; D004347:Drug Interactions; D005442:Flumazenil; D005795:Generalization, Stimulus; D008297:Male; D010424:Pentobarbital / Q000008:administration & dosage*; D011720:Pyrazoles / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects
D001570:Benzodiazepinones; D011720:Pyrazoles; D011963:Receptors, GABA-A; D005442:Flumazenil; D002707:Chlordiazepoxide; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; D010424:Pentobarbital