Ethanol and Ro 15-4513: behaviour maintained by operant procedures (DRL-72s and PTZ-drug discrimination) in rats

The proposed amethystic imidazobenzodiazepine Ro 15-4513 and ethanol (ETOH) were examined in rats using two operant procedures, differential reinforcement of low rates of responding (DRL), and drug discrimination learning (DDL). In the first bar-pressing responses occurring 72 s or longer after the last reinforcement were rewarded; responses occurring earlier reset the time schedule. In the latter, animals were trained to discriminate between the effects of the analeptic pentylenetetrazole (PTZ) and the non-drug condition; the schedule of reinforcement was FR-10. Water was the reinforcer. A dose of 1000 mg/kg ETOH decreased the rate of bar pressing in the DRL experiment; doses of 300 and 560 mg/kg ETOH did not. The decrease was not attenuated by Ro 15-4513. No significant deviations from baseline responding occurred with Ro 15-4513 (1, 3 10 mg/kg). The number of reinforcements increased significantly after ETOH (1000 mg/kg), but not after Ro 15-4513. Combinations of the two agents produced increases in the number of reinforcements. Changes in DRL behaviour induced by diazepam (1 and 10 mg/kg) were normalized by 3 mg/kg Ro 15-4513. In DDL, Ro 15-4513 (10 mg/kg) substituted for PTZ; ETOH did not. Diazepam and Ro 15-1788 attenuated the response generalization from Ro 15-4513 to PTZ; ETOH did not. There was a dose-related increase in the time to complete the DDL tests after ETOH treatment; addition of Ro 15-4513 increased the time further. In conclusion, antagonism between Ro 15-4513 and ETOH did not occur in the present studies; data are furthermore consistent with the view that Ro 15-4513 acts as a partial inverse benzodiazepine agonist.