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.
Cole
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Psychology Department, Rutgers University, Camden, NJ 08102.
D000818:Animals; D002707:Chlordiazepoxide / Q000037:antagonists & inhibitors*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects; D005442:Flumazenil / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D005442:Flumazenil; D002707:Chlordiazepoxide