Behavioral effects of the pyrazoloquinoline CGS 9896: agonist and antagonist actions in squirrel monkeys

The behavioral effects of 2-p-chlorophenylpyrazolo[4,3-c]quinolin-3(5H)-one (CGS 9896) were compared with those of lorazepam and zopiclone in squirrel monkeys. Two groups of monkeys were trained to respond under a fixed-interval schedule of food presentation. In one group, responding was suppressed (punished) by superimposing a fixed-ratio schedule of response-produced shock. Dose-effect curves were determined for all three drugs by administering cumulative doses i.v. during timeout periods that preceded sequential components of the fixed-interval schedule. Low and intermediate doses of CGS 9896 (0.03-3.0 mg/kg), lorazepam (0.03-0.3 mg/kg) or zopiclone (0.1-1.0 mg/kg) produced dose-related increases in the rates of both suppressed and nonsuppressed responding. The maximal increases in response rates produced by CGS 9896 were usually less than those produced by either lorazepam or zopiclone. Pretreatment with the benzodiazepine antagonist Ro 15-1788 antagonized the increases in suppressed and nonsuppressed response rates produced normally by intermediate doses of CGS 9896, lorazepam or zopiclone, suggesting that the rate-increasing effects of the three drugs are mediated similarly. CGS 9896 was studied additionally for antagonist activity by administering selected doses before lorazepam or zopiclone. Pretreatment with a high dose of CGS 9896 (5.0 mg/kg) antagonized the rate-increasing effects of both lorazepam and zopiclone, suggesting that CGS 9896 has antagonist effects in addition to its agonist effects at benzodiazepine recognition sites.