Metabolic and behavioral changes induced by chronic treatment with dexamethasone in mice: differential effects in males and females

Abstract

Stress is characterized as one of the main factors that contribute to the development of psychiatric and metabolic diseases. Through excessive activation of the hypothalamic-pituitary-adrenal (HPA) axis, and the resulting release of cortisol (in humans) or corticosterone (in rodents), the chronic increase in these hormones has been shown to contribute significantly to the development of depression and type 2 diabetes. Given the increase in mental disorders and metabolic pathologies in recent years, a better understanding of the factors contributing to the development of these conditions has become an important object of study. Here, we evaluated the behavioral and metabolic effects of chronic administration of dexamethasone, at a dose of 4 mg/kg, for 21 days, in male and female mice. The results indicate that dexamethasone treatment resulted in anxious like-behavior and passive stress-coping behavior in male and female mice. Moreover, we uncover sex-specific outcomes of chronic dexamethasone treatment on metabolic phenotypes in mice. Treatment with dexamethasone specifically resulted in a significant weight loss and increased plasma concentration of total proteins in male mice. Also, dexamethasone-induces hypercholesterolemia was observed in both male and female mice, although it did not impact glucose levels and glucose tolerance after glucose loading. The present study reproduced some metabolic and behavioral effects observed in humans exposed to excess glucocorticoids, providing preclinical evidence for future studies.