ANATOMICAL SPECIFICITY AND TIME-DEPENDENCE OF CHLORDIAZEPOXIDE-INDUCED SPATIAL MEMORY IMPAIRMENTS

Injection of the benzodiazepine (BDZ) chlordiazepoxide (CDP) into the medial septum (MS) produced a dose-dependent retrograde working memory deficit in a delayed non-match-to-sample radial-arm maze task. CDP (3 0 nmol; 10 mu g) decreased the number of correct choices and increased the number of errors without altering latency to make arm choices. Th e effects of CDP were site specific; injection into regions proximate to the MS, including the lateral septum, the anterior cingulate, and t he nucleus basalis magnocellularis, did not affect any index of perfor mance. The second experiment demonstrated that CDP impaired working me mory only when rats were injected either 0 or 60 min, but not 15, 30, or 45 min, following training. The MS appears (a) to contribute to bot h early (encoding/maintenance) and late (retrieval/utilization) phases of working memory and (b) to be a critical site of action for BDZ-ind uced deficits in spatial working memory.