title: Differential diazepam-antagonist effects of the benzodiazepine receptor ligand CGS 9895 in rodents.
abstract: CGS 9895, a pyrazoloquinolone benzodiazepine receptor ligand, was administered alone and concomitantly with diazepam in order to assess its agonist and diazepam-antagonist properties on various behaviors in rodents. In mice, CGS 9895 neither potentiated nor blocked the convulsant effects of pentylenetetrazole. However, doses of 3.0 and 10 mg/kg of CGS 9895 i.p. produced dose-related antagonism of the anticonvulsant effects of diazepam against pentylenetetrazole (80 mg/kg i.p.). In rats, diazepam produced dose-related increases in ataxia as measured on the rotarod. CGS 9895 (0.3-10 mg/kg i.p.) was without effect on performance on the rotarod, but produced dose-related parallel shifts to the right in the diazepam dose-effect curve. Also in rats, behavior was maintained under a multiple schedule where in one component every 20th response resulted in water presentation (unpunished behavior) and in a second component every 20th response resulted in both shock and water presentation (punished behavior). CGS 9895 (0.3-30 mg/kg i.p.) was without significant effect on either punished or unpunished responding. Increasing doses of diazepam (0.1-10 mg/kg p.o.) first increased and then decreased rates of punished responding but only decreased rates of unpunished responding. CGS 9895 (3.0 mg/kg i.p.) neither potentiated nor antagonized diazepam. In another group of rats, behavior was maintained under a multiple fixed-interval 5 min fixed-ratio 20 response schedule of water presentation. CGS 9895 (0.3-30 mg/kg i.p.) did not affect performance under this schedule. Diazepam (0.3-30 mg/kg p.o.) primarily decreased rates under the fixed-ratio schedule, but increasing doses first increased and then decreased rates under the fixed-interval schedule.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects; D003975:Diazepam / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D008024:Ligands; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D011678:Punishment; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011963:Receptors, GABA-A / Q000187:drug effects*
chemical_list: D000927:Anticonvulsants; D008024:Ligands; D011720:Pyrazoles; D011963:Receptors, GABA-A; C039232:2,5-dihydro-2-(4-methoxyphenyl)-3H-pyrazolo(4,3-c)quinolin-3-one; D003975:Diazepam