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 (30 nmol; 10 micrograms) decreased the number of correct choices and increased the number of errors without altering latency to make arm choices. The effects of CDP were site specific; injection into regions proximate to the MS, including the lateral septum, the anterior cingulate, and the nucleus basalis magnocellularis, did not affect any index of performance. The second experiment demonstrated that CDP impaired working memory 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 both early (encoding/ maintenance) and late (retrieval/utilization) phases of working memory and (b) to be a critical site of action for BDZ-induced deficits in spatial working memory.