Behavioral effects of zopiclone, CL 218,872 and diazepam in squirrel monkeys: antagonism by Ro 15-1788 and CGS 8216.

The effects of zopiclone, CL 218,872 and diazepam were compared in squirrel monkeys trained to respond under a fixed-interval (FI) schedule of food presentation. Dose-response curves were determined for each drug by administering cumulative doses i.v. during timeout periods that preceded sequential components of the FI schedule. Low and intermediate doses of zopiclone (0.03-1.0 mg/kg), CL 218,872 (0.3-3.0 mg/kg) or diazepam (0.1-1.0 mg/kg) produced dose-related increases in the rate of FI responding. The highest doses of diazepam (10.0 mg/kg) and CL 218,872 (30.0 mg/kg), but not of zopiclone (30.0 mg/kg), decreased FI responding markedly. Doses of zopiclone, CL 218,872 and diazepam that were effective in increasing FI responding were similar to the doses reported previously to increase suppressed (punished) responding in squirrel monkeys. Pretreatment with the benzodiazepine antagonists Ro 15-1788 or CGS 8216 (1.0 or 3.0 mg/kg) reduced or eliminated the increases in FI responding produced normally by intermediate doses of zopiclone, CL 218,872 or diazepam, suggesting that the rate-increasing effects of the three agonists reflect similar actions at benzodiazepine recognition sites. In contrast, Ro 15-1788 and CGS 8216 were less effective or ineffective in attenuating the marked decreases in FI responding produced by the highest doses of CL 218,872 or diazepam, suggesting that the rate-decreasing effects of these agonists are mediated differently from their rate-increasing effects.