Effects of acute daily administration of diazepam on spatial learning and working memory

This study evaluated the acute or daily effects of diazepam (DZP) on the acquisition and performance of rats in an 8-arm radial maze. Male Wistar rats (200-250 g) were divided into three groups: saline-saline (SS), saline-DZP (SD) and DZP-DZP (DD). The SS group always received intraperitoneal (i.p.) saline (SAL) in daily or acute treatments. The SD group received SAL (i.p.) daily during the task acquisition (30 days), DZP (2.5 mg/kg, i.p.) 45 min before the acute 5 s and 1 h delay tests, and it also received DZP (10 mg/kg, i.p.) for 70 days. The DD group received DZP (10 mg/kg, i.p.) daily during 30 days in the task acquisition, DZP (2.5 mg/kg, i.p.) 45 min before the acute 5 s and 1 h delay tests and further received DZP (10 mg/kg, i.p.) for an additional 70 days. Our results showed that as compared to control (SS group), 8-10 h prior administration of a single daily dose of DZP (10 mg/kg) did not alter the learning and the performance of short- (5 s delay) and long-term (1 h delay) working memory. However, the acute administration of DZP (2.5 mg/kg) impaired the performance of the short delay task (5 s delay) in animals previously exposed (DD group) or not (SD group) to daily DZP treatment. Therefore, the acute administration of an anxiolytic dose of DZP (2.5 mg/kg) produced a significant impairment of short-term working memory, even in animals exposed to daily DZP treatment for a long time.