Effect of chronic corticosterone administration on acute stress-mediated gene expression in the cortex and hippocampus of male mice

Corticosterone plays an important role in the stress response, physiological regulation, and development of stress-related psychiatric disorders. Although several studies have demonstrated that chronic corticosterone induces anxiety- or depressive-related behaviors in mice, it remains unclear whether chronic corticosterone administration affects gene expression in the brain during the stress response. This study investigated whether chronic corticosterone administration has a significant effect on stress-related gene expression in the brain. Therefore, mice were chronically treated with corticosterone in drinking water and gene expression was analyzed by quantitative PCR (qPCR). Moreover, restraint stress was acutely applied as a novel stressor in mice chronically treated with corticosterone in the cortex and hippocampus. We initially found that chronic corticosterone administration altered glucocorticoid signaling-mediated gene expression, such as FK506 binding protein 5 (Fkbp5) and glucocorticoid-inducible kinase 1 (Sgk1), in the cortex and hippocampus of mice. Next, we found that restraint stress exposure elevated Fkbp5 expression in the vehicle group; however, chronic corticosterone administration occluded further induction of Fkbp5 expression after restraint stress exposure. In addition, pro-inflammatory cytokines tumor necrosis factor α (Tnfa) and interleukin-1β (Il1b) mRNA expression in the cortex and hippocampus were remarkably enhanced by restraint stress in corticosterone-treated mice, but not in the vehicle group. Collectively, our results demonstrated that chronic corticosterone administration modulates glucocorticoid signaling and uncovered the robust induction of pro-inflammatory cytokines after restraint stress exposure in chronically corticosterone-treated mice. These mechanisms may be involved in the molecular basis for the onset of stress-related mental illnesses.