Neuroendocrine stress reactivity of male C57BL/6N mice following chronic oral corticosterone exposure during adulthood or adolescence

Adolescence is associated with the maturation of the hypothalamic-pituitary-adrenal (HPA) axis, the major neuroendocrine axis mediating the hormonal stress response. Adolescence is also a period in development marked by a variety of stress-related vulnerabilities, including psychological and physiological dysfunctions. Many of these vulnerabilities are accompanied by a disrupted HPA axis. In adult mice, a model of disrupted HPA function has been developed using oral chronic corticosterone administration via the drinking water, which results in various physiological and neurobehavioral abnormalities, including changes in stress reactivity and anxiety-like behaviors. In an effort to further complement and extend this model, we tested the impact of HPA disruption in adolescent mice. We also examined whether this disruption led to different outcomes depending on whether the treatment happened during adolescence or adulthood. In the current set of experiments, we exposed adult (70 days of age) or adolescent (30 days of age) male C57BL/6N mice to 4 weeks of either 0 or 25 mu g/m1 oral corticosterone via their drinking water. We measured body weight during treatment and plasma corticosterone levels and activation of the paraventricular nucleus (PVN), as indexed by FOS immunohistochemistry, before and after a 30 min session of restraint stress. Our data indicate that adolescent animals exposed to chronic corticosterone showed weight loss during treatment, an effect not observed in adults. Further, we found stress failed to elevate plasma corticosterone levels in treated mice, regardless of whether exposure occurred in adulthood or adolescence. Despite this reduced hormonal responsiveness, we found significant neural activation in the PVN of both adult- and adolescent-treated mice, indicating a dissociation between stress-induced peripheral and central stress responses following chronic corticosterone exposure. Moreover, stress-induced neural activation in the PVN was unaffected by chronic corticosterone treatment in adult animals, but led to a hyper responsive PVN in the corticosterone-treated adolescent animals, suggesting an age-specific effect of corticosterone treatment on later PVN stress reactivity. Together, these experiments highlight the influence of developmental stage on somatic and neuroendocrine outcomes following chronic HPA disruption by noninvasive, oral corticosterone treatment. Given the substantial vulnerabilities to HPA dysfunctions during adolescence this model may prove useful in better understanding these vulnerabilities.