Discrimination of Ro 11-6896, chlordiazepoxide and ethanol in gerbils: generalization and antagonism tests

Abstract

Separate groups of gerbils were trained in a T-maze to discriminate between either: (1) the 1,4-benzodiazepine Ro 11-6896 (1 mg/kg), (2) chlordiazepoxide (25 mg/kg) or (3) ethanol (2,000 mg/kg) and vehicle. Thus, the respective training condition served as a discriminative stimulus guiding choice behavior. A degree of generalization which was enhanced by increasing injection-test intervals occurred between ethanol and the benzodiazepines. Ro 15-1788 markedly attenuated the cue properties of the benzodiazepines, but not that of ethanol. Additional tests in the Ro 11-6896 group showed that this discrimination was stereoselective but not stereospecific in that the isomer Ro 11-6893 generalized to Ro 11-6896 at a dose of 10 mg/kg but not at 1 mg/kg; Ro 15-1788 attenuated this generalization. Diazepam (3 mg/kg) generalized to Ro 11-6896 whereas the structurally related Ro 5-4864 (3 mg/kg and 30 mg/kg) did not. In separate tests of open-field activity and temperature recording Ro 15-1788 significantly attenuated the effects of Ro 11-6896 (1 mg/kg) and Ro 11-6893 (10 mg/kg).