Cueing effects of anxiolytic benzodiazepines (DZP and Ro 11-3128): stereospecificity and antagonism by the convulsant benzodiazepine Ro 5-3663

Two groups of gerbils were trained in a T-maze to discriminate between the vehicle condition (4 ml/kg) and either of the benzodiazepine (BDZ) agonists diazepam (DZP) and Ro 11-3128; administration (5.6 mg/kg) was IP 5 min prior to training onset. Once trained, novel doses and drugs were assessed in test sessions interposed between the regular training days. A dose-related generalization effect occurred with both compounds (range 0.1-5.6 mg/kg), the effect being similar at both the 5 and 15 min test intervals; the two intervals were evaluated after a single injection. The lack of generalization of Ro 11-3624 (range 5.6-56 mg/kg) indicates a stereoisomeric separation of BDZ agonist activity. Ro 5-4864 (range 17.5-56 mg/kg), an agent chemically/structurally related to DZP, did not produce DZP responding at either of the two test inverals; clear-cut convulsant activity occurred at the 15 min interval. The convulsant BDZ compound Ro 5-3663 (3 and 10 mg/kg) antagonized the DZP stimulus irrespective of whether Ro 5-3663 was given either prior to, simultaneously with, or shortly after the DZP injection.