The primary objective of the present proposal is to elucidate the central mechanisms underlying the benzodiazepine-induced impairment of successive discrimination, by determining the effects of Ro 15-1788 (a central benzodiazepine receptor antagonist) on such impairment. Using Sprague-Dawley rats as subjects, a series of experiments will be conducted: a) to determine the effects of Ro 15-1788 on chlordiazepoxide-induced impairment in the acquisition and performance of successive discrimination; b) to determine the generality of benzodiazepine- induced impairment of successive discrimination by investigating the effects of diazepam on the acquisition and performance of such a task; and finally c) to determine the effects of Ro 15-1788 on diazepam-induced impairment in the acquisition and performance of successive discrimination. It is hypothesized that Ro 15-1788 will block or reverse the impairment of successive discrimination by chlordiazepoxide and diazepam, thereby providing evidence for the involvement of central benzodiazepine receptor sites in the mediation of such impairment. However, the nature of the reversal may differ with acquisition and performance stages of learning. The results could lead to a safer and more efficacious use of benzodiazepines in the treatment of human anxiety and have significance in relationship to predrug/postdrug protocol and possible differences in mediation mechanisms with different stages (acquisition and performance) of learning.
| Cole, S O (1990) Diazepam-induced impairment of a go-no go successive discrimination. Behav Neural Biol 53:371-7 |
| Cole, S O (1988) Dose-dependent reversal of chlordiazepoxide-induced discrimination impairment by Ro 15-1788. Psychopharmacology (Berl) 96:458-61 |
