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The dose-response relationships of diazepam and several of its metabolites were determined in rats trained to discriminate diazepam (3 mg/kg) from saline in a two-lever operant choice task. Generalization of the diazepam stimulus was found to occur with temazepam and oxazepam, which were nearly equipotent with diazepam, and also with desmethyldiazepam, which was about half as potent as diazepam. The hydroxylated metabolites, 4'-hydroxydiazepam and 4'-hydroxydesmethyldiazepam were inactive in doses up to 12 mg/kg. These results show that some diazepam metabolites are quite potent behaviorally and indicate the possibility that these metabolites may contribute to the pharmacological effect of diazepam in vivo.
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