CGS 8216: agonist and diazepam-antagonist effects in rodents

CGS 8216, a pyrazoloquinolinone benzodiazepine receptor ligand, was administered alone and concomitantly with diazepam in order to assess its agonist and diazepam-antagonist properties on several behaviors in rodents. In mice, CGS 8216 (i.p.) potentiated the convulsant effects of pentylenetetrazole. Moreover, doses of 1.0 to 10 mg/kg of CGS 8216 produced dose-related antagonism of the anticonvulsant effects of diazepam. In rats, CGS 8216 (0.3-3.0 mg/kg) was without effect on the Rotarod, but produced dose-related, nonparallel 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 component) and in a second component every 20th response resulted in both footshock and water presentation (punished component). CGS 8216 produced dose-related decreases in response rates in both components, but was approximately 10-fold more potent in decreasing rates of punished responding. These effects were blocked by the benzodiazepine antagonist Ro 15-1788 (30 mg/kg i.p.). 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 8216 produced a dose-related antagonism of the rate-increasing, but had little effect on the rate-decreasing, effects of 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 8216 produced a dose-related decrease in response rates in both components, but these effects were not blocked by Ro 15-1788 (30 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)