Dose-dependent reversal of chlordiazepoxide-induced discrimination impairment by Ro 15-1788

Chlordiazepoxide (10 mg/kg), administered on eight successive acquisition sessions, impaired a light-cued, successive discrimination in male Sprague-Dawley rats by increasing the number of incorrect responses. The benzodiazepine receptor antagonist Ro 15-1788 (5 and 10 mg/kg) reversed the discrimination impairment and reduced the number of incorrect responses in a generally dose-dependent manner when co-administered with chlordiazepoxide. These findings suggest that the impairment of successive discrimination by chlordiazepoxide is mediated by central benzodiazepine receptor sites. When administered alone, however, the 10 mg/kg dose of Ro 15-1788 (but not the 5 mg/kg dose) produced a mild benzodiazepine-like impairment in discrimination, which was accompanied by a small but significant increase in incorrect responses. These findings suggest that Ro 15-1788 may also have some intrinsic action of its own, which needs to be assessed independently of its use as a mediational research tool.