Prepubertal and adult male rats differ in the degree and pattern of stress reactive neurons in brain regions that project to the paraventricular nucleus of the hypothalamus.

The hormonal stress response, mediated by the hypothalamic-pituitary-adrenal (HPA) axis, shows greater responsiveness to various stressors in prepubertal compared to adult animals. Though the implications of this age-related change are unclear, this heightened reactivity might contribute to the increase in stress-related dysfunctions observed during adolescence. Interestingly, prepubertal animals show greater stress-induced neural activation compared to adults in the paraventricular nucleus of the hypothalamus (PVN), the area responsible for initiating the hormonal stress response. Thus, it is possible that direct afferents to the PVN, such as the anterior bed nucleus of the stria terminalis (aBST), nucleus of the solitary tract (NTS), posterior BST (pBST), medial preoptic area (MPOA), and dorsomedial nucleus (DMN), contribute to this age-dependent change in reactivity. To investigate these possibilities, two separate experiments were conducted in prepubertal (30 days old) and adult (70 days old) male rats using the retrograde tracer, Fluoro-Gold (FG), and FOS immunohistochemistry to study neural connectivity and activation, respectively. Though there was no difference in the number or size of FG-positive cells in the PVN afferents we examined, we found a significantly greater number of stress-induced FOS-like-positive cells in the aBST and significantly fewer in the DMN in prepubertal compared to adult animals. Together these data suggest that functional, instead of structural, changes in nuclei that project to the PVN may lead to the greater PVN stress responsiveness observed prior to adolescence. Furthermore, these data indicate that nuclei known to directly modulate HPA stress responsiveness show differential activation patterns before and after adolescent development.

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

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.