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

Abstract

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.