Lorazepam and pentobarbital drug discrimination in baboons: cross-drug generalization and interaction with Ro 15-1788.

Four baboons were trained to discriminate lorazepam (1.0 mg/kg i.m.) and two baboons were trained to discriminate pentobarbital (5.6 mg/kg i.m.) in a two-lever drug discrimination procedure. Food delivery depended on 20 consecutive responses on one lever in sessions preceded by an injection of the training drug and on 20 consecutive responses on the other lever after no drug. All baboons reliably completed 100% of the response runs on the appropriate lever in training sessions. Test sessions were conducted in which a drug dose different from the training dose was injected and 20 consecutive responses on either lever produced food. Drug lever responding occurred after a range of lorazepam and diazepam doses in both lorazepam- and pentobarbital-trained baboons. Drug lever responding also occurred after a range of doses of pentobarbital in the pentobarbital-trained baboons but in only one of the four lorazepam-trained baboons. Ro 15-1788 (0.1-1.0 mg/kg p.o.) antagonized the effect of lorazepam but had no effect on the pentobarbital discriminative stimulus. The asymmetrical generalization with lorazepam and pentobarbital suggests a specificity of discriminative stimulus effects that heretofore have not been documented in drug discrimination experiments with benzodiazepines and barbiturates. The selective antagonism of lorazepam by the benzodiazepine-receptor antagonist Ro 15-1788 suggests that the lorazepam but not the pentobarbital discriminative stimulus is mediated at the benzodiazepine receptor.