Distinctive behavioral effects of the pyrazoloquinoline CGS 8216 in squirrel monkeys

The behavioral effects of the pyrazoloquinoline CGS 8216 were studied in squirrel monkeys trained to respond under a fixed-interval (FI) schedule of food presentation. Dose-effect curves were determined by administering cumulative doses IV during timeout periods that preceded sequential components of the FI schedule. CGS 8216 (0.1-3.0 mg/kg) produced dose-related decreases in the rate of FI responding. In comparison, diazepam (0.1-3.0 mg/kg) had biphasic effects under identical conditions: intermediate doses increased the rate, whereas high doses decreased the rate of FI responding. Pretreatment with the benzodiazepine antagonist Ro 15-1788 (3.0 or 5.6 mg/kg) attenuated the decreases in response rate normally produced by high doses of CGS 8216. The behavioral effects of CGS 8216 were not altered systematically by pretreatment with either diazepam (0.3-3.0 mg/kg) or the alpha 2-adrenergic agonist clonidine (0.01-0.03 mg/kg). The results suggest that CGS 8216 has benzodiazepine inverse agonist effects on schedule-controlled behavior of squirrel monkeys. CGS 8216 can, however, be distinguished from inverse agonists of the beta-carboline type on the basis of its effects in the presence of diazepam or clonidine.