Faculty Bibliography

Following an acute stressor, pre-adolescent rats exhibit a protracted hormonal response compared to adults, while after repeated exposure to the same stressor (i.e., homotypic stress) prepubertal males fail to habituate like adults. Though the neurobehavioral implications of these changes are unknown, studying pubertal shifts in stress reactivity may help elucidate the mechanisms that underlie the increase in stress-related psychological and physiological disorders often observed during adolescence. Here, we investigated hormonal, behavioral, and neural responses of prepubertal (30d) and adult (77d) male rats before, during, or after acute stress (restraint), homotypic stress (repeated restraint) or heterotypic stress (repeated cold exposure followed by restraint). We found that prepubertal males exhibit prolonged corticosterone responses following acute and heterotypic stress, and higher adrenocorticotropic hormone and corticosterone responses after homotypic stress, compared to adults. Despite these significant age-dependent changes in hormonal responsiveness, we found that struggling behavior during restraint was similar at both ages, such that both prepubertal and adult animals exposed to homotypic stress struggled less than animals exposed to either acute or heterotypic stress. Across these different stress paradigms, we found greater neural activation, as indexed by FOS immunostaining, in the prepubertal compared to adult paraventricular nucleus of the hypothalamus, a nucleus integral for initiating the hormonal stress response. Interestingly, however, we did not find any influence of pubertal development on stress-induced activation of the posterior paraventricular thalamic nucleus, a brain region involved in experience-dependent changes in stress reactivity. Collectively, our data indicate that prepubertal and adult males display divergent hormonal, behavioral, and neural responses following a variety of stressful experiences, as well as a distinct dissociation between hormonal and behavioral reactivity in prepubertal males under homotypic conditions.

Prepubertal rats display heightened hormonal stress reactivity compared with adults in that levels of ACTH and corticosterone take twice as long (i.e. 40-60 min) to return to baseline following an acute stressor. Despite this substantial change in stress responsiveness, and the critical nature of the adolescence period of development, the maturation of the hormonal stress response from the time of pubertal onset to adulthood has not been thoroughly investigated. To examine this, we measured ACTH, corticosterone, and testosterone in 30-, 40-, 50-, 60-, and 70-day-old (i.e. spanning pubertal and adolescent development) male rats before and after a 30 min session of restraint stress. We found that the adult-like ACTH stress response develops between 50 and 60 days of age, while the corticosterone response changes between 30 and 40 days of age. We also found that adrenal corticosterone concentrations paralleled the plasma corticosterone response following restraint, suggesting that stress-induced adrenal corticosterone synthesis decreases during adolescent development and may, at least in part, contribute to the differential stress response observed before and after puberty. Finally, stress leads to increases in testosterone secretion, but only after 50 days of age. Collectively, these results indicate that shifts in hormonal stress responses occur throughout adolescent maturation and that these responses show distinct developmental profiles.