A lack of tolerance to the anxiolytic effects of diazepam on the plus-maze: comparison of male and female rats

Rationale: The demonstration of tolerance to the anxiolytic effects of benz odiazepines remains inconsistent. Objectives: The present study tested the hypothesis that intact and gonadectomized male and female rats might exhibi t differential tolerance to the anxiolytic effects of diazepam (DZ). Method s: Following acute (3 days) or chronic (3 weeks) DZ exposure, all animals w ere tested on the elevated plus-maze and immediately sacrificed for analysi s of corticosterone, adrenocorticotropin hormone, estrogen and progesterone levels in serum. In experiment 2, following acute or chronic DZ exposure, animals were treated with a DZ challenge dose on the test day. Results: In experiment 1, both acute and chronic DZ treatment similarly enhanced percen tage open arm time and entries, regardless of the hormonal status of the an imal. The results of experiment 2 showed that both acute and chronic DZ-tre ated animals exhibited a significantly higher percentage open arm time than control animals after the DZ challenge dose, and males and females did not differ in their responses to DZ exposure. Conclusions: The findings from t hese experiments suggest that tolerance to the anxiolytic effects of DZ did not develop in males or females, and that the hormonal status of the anima l does not significantly alter the anxiolytic effects of DZ following eithe r acute or chronic exposure. Following plus-maze exposure, females had sign ificantly higher corticosterone levels than males and acute DZ treatment di minished this stress response.