Age-dependent changes in hormonal stress reactivity following repeated restraint stress throughout adolescence in...

Stress-related psychological dysfunctions show a marked increase during adolescence, yet the mechanisms that mediate these vulnerabilities are unknown. Notably, however, adolescence is associated with changes in hormonal stress reactivity mediated by the hypothalamic-pituitary-adrenal (HPA) axis, which might contribute to these dysfunctions. Specifically, pre-adolescent animals display prolonged stress-induced HPA responses compared to adults. Previous experience with stressors further modify these changes in stress reactivity, such that repeated exposure to the same stressor results in an augmented HPA response prior to adolescence, but a habituated response in adulthood. It is unclear when during adolescence the habituated, adult-like response develops to a repeated stressor. Using male rats at various ages that span adolescence (30-70 days of age), we show that by mid-adolescence (i.e. 42 days of age), animals show neither a facilitated nor a habituated HPA hormonal response following four days of repeated restraint stress (4RS) compared to a single restraint session (1RS). We also show that the habituated HPA response to 4RS develops between late-adolescence and young adulthood (i.e. between 56 and 70 days of age, respectively). Further, we find age- and experience-dependent changes in progesterone and testosterone secretion, indicating that the interaction between development and experience affects stress-induced hormonal responses outside of canonical HPA-related hormones. Despite these hormonal differences mediated by age and experience, repeated restraint stress resulted in decreased fecal boli production at all four ages, suggesting dissociation between hormonal and autonomic reactivity during adolescence. These data indicate that HPA plasticity is significantly affected by adolescence and that a habituated hormonal response to homotypic stress does not occur until young adulthood. A greater appreciation of these changes in stress reactivity will contribute to our understanding of the psychological vulnerabilities often associated with stressful adolescence.