Stress-Induced Activation of Orexin-A Neurons in the Lateral Hypothalamus Is Similar in Prepubertal and Adult Male and Female Rats despite Age-Dependent Differences in Hormonal Stress Reactivity.

Pubertal development is associated with changes in hypothalamic-pituitary-adrenal (HPA) axis reactivity, which may contribute to the increase in stress-related vulnerabilities observed during adolescence. In particular, prepubertal rats show significantly protracted stress-induced HPA responses compared to adults. However, the neuroendocrine mechanisms responsible for this developmental change are unclear. In adults, the orexigenic neuropeptide orexin-A has been shown to be a potent modulator of HPA reactivity, and activation of orexin-A neurons aligns with the magnitude of the hormonal stress response. However, it is currently unknown whether pubertal differences in HPA reactivity are associated with changes in orexin-A neurons. We examined the hormonal stress response and the number of activated orexin-A neurons in the lateral hypothalamus by co-labeling with c-Fos, a marker of cellular activation, before, during, or after stress exposure in prepubertal (30 days of age, 30 d) and adult (70 d) male and female rats. The number of immunoreactive orexin-A neurons was also quantified in prepubertal (30 d), mid-pubertal (45 d) and adult (70 d) males and females. We found significantly prolonged stress-induced hormonal responses in prepubertal males and females compared to their adult counterparts. However, we found no developmental differences in either the number of orexin-A cells or their stress-induced activation in either sex. These data suggest minimal association between stress-induced activity of orexin-A neurons and pubertal-related differences in hormonal stress reactivity. However, these data indicate that the number of orexin-A cells is relatively stable throughout adolescent development and that orexin-A neurons are sensitive to stressors prior to pubertal maturation.