Discriminative stimulus properties of chlordiazepoxide and zolpidem. Agonist and antagonist effects of CGS 9896 and ZK 91296.

In previous studies the effects of CGS 9896, a pyrazoloquinoline ligand at benzodiazepine receptors, in rats trained to discriminate benzodiazepines from vehicle, have been variable. The present experiment confirmed that this compound produced responding on the drug-lever in rats trained to discriminate 5 mg/kg of chlordiazepoxide from saline, and showed that CGS 9896 did not antagonise the effect of chlordiazepoxide in this test. In contrast, CGS 9896 antagonised the stimulus properties of zolpidem (2 mg/kg), a non-benzodiazepine hypnotic, which displaces benzodiazepines from their binding sites. The drug CGS 9896 also antagonised responding on the drug-lever produced by chlordiazepoxide in rats trained with zolpidem. The beta-carboline, ZK 91296, produced effects similar to those of CGS 9896, giving rise to responding on the drug-lever in rats trained with chlordiazepoxide and antagonising the zolpidem cue. These results demonstrate the mixed agonist-antagonist effects of CGS 9896 and ZK 91296 and suggest that the stimulus properties of chlordiazepoxide and zolpidem may be mediated by different sub-types of benzodiazepine receptors.