Behavioral effects of nonbenzodiazepine anxiolytic drugs: a comparison of CGS 9896 and zopiclone with chlordiazepoxide

Abstract

Zopiclone and CGS 9896 are two nonbenzodiazepine compounds which have been shown to displace benzodiazepines from their binding sites. The present study compared the behavioral effects of these two compounds in rats with those of chlordiazepoxide. The three drugs produced dose-related increases in punished drinking as did pentobarbital and meprobamate but not PK 9084, which also acts at benzodiazepine binding sites, or buspirone. Rates of lever pressing suppressed by punishment were also increased by chlordiazepoxide and zopiclone. CGS 9896 exerted a similar although less marked effect. Lever pressing maintained by a differential reinforcement of low rate 18-sec schedule of milk presentation was increased by low doses of chlordiazepoxide and zopiclone and decreased by higher doses leading to dose-related reductions in numbers of reinforcers obtained. CGS 9896 also reduced number of reinforcers but without affecting rate of responding. In rats trained to discriminate a dose of chlordiazepoxide from saline, chlordiazepoxide, zopiclone, pentobarbital and meprobamate produced chlordiazepoxide-appropriate responding. CGS 9896 also produced chlordiazepoxide-appropriate responding at a wide range of doses although the stimulus properties of this compound appeared to be weaker than those of the other active drugs. Chlordiazepoxide and zopiclone produced dose-related increases in food intake in food-deprived rats. CGS 9896 had similar effects at low doses but its effects were less consistent at higher doses. Thus, zopiclone has a behavioral profile very similar to that of chlordiazepoxide. Although many of the effects of CGS 9896 were similar to those of chlordiazepoxide, a number of differences were also observed.