Chronic Corticosterone Administration Effects on Behavioral Emotionality in Female C57BL6 Mice

Understanding the pathophysiology of affective disorders and their treatment relies on the availability of experimental models that mimic aspects of the disease. Most of the studies on depressive disorders are conducted with male rodents, mostly because including females in protocols is more difficult. Indeed, there is a complex series of changes in the brain of females due to the estrous cycle, adding an important variability factor to the disease. However, twice as many women as men have a lifetime diagnosis of major depressive disorder (MDD), so we need to develop reliable female models of depression to improve our understanding of this disease. Here, we describe the effects of chronic corticosterone administration (CORT) on female mice, a procedure known to enhance behavioral emotionality in male mice. A dose-response study showed that 4 weeks of CORT exposure at 35 mu g/ml in the drinking water enhanced the emotionality score of female mice, but with a very small size effect. Tests of longer treatment duration failed to potentiate the behavioral effects of CORT. As some steps of adult hippocampal neurogenesis are known to be sensitive to chronic CORT exposure, cell proliferation and survival, as well as neuronal maturation in the dentate gyrus of the hippocampus, analyses revealed no effect of chronic CORT exposure in female mice. Overall, this study showed that female C57BL6 mice are insensitive to chronic CORT as a way to model anxio-depressive-like behavior.