Pubertal development is marked by dramatic shifts in stress reactivity. For instance, in response to an acute stressor, adrenocorticotropic hormone (ACTH) and corticosterone levels in prepubertal animals remain elevated for twice as long compared to adults. In addition to these developmental changes in stress responsiveness, experiential factors also differentially influence HPA reactivity in adolescent and adult animals. Specifically, repeated exposure to a homotypic stressor (i.e., same stressor) results in a habituated hormonal response in adults, but an exaggerated hormonal response in prepubertal animals. A greater appreciation of the factors that mediate these pubertal shifts in stress reactivity is imperative, as repeated stressful experiences during pubertal maturation are clearly implicated in many of the physiological and psychological vulnerabilities (e.g., obesity, drug abuse, depression, anxiety) associated with this stage of development. Therefore, the goal of the experiments in this proposal is to begin to expand our fundamental understanding of the neural substrates involved in mediating these developmental and experiential changes in stress reactivity. To these ends, two Aims are proposed.
Aim I will test the hypothesis that the pattern of neural activation in response to repeated stress will be different before and after pubertal development. Specifically, prepubertal and adult rats will be exposed to a diverse set of stress paradigms and immediate-early gene expression will be measured in brain areas important in experience-dependent changes in HPA function to begin mapping sites of differential neural activation between these two stages of development.
Aim II will test the hypothesis that the posterior paraventricular thalamic nucleus (pPVT) plays a direct role in the unique experience-dependent changes in stress reactivity exhibited by pubertal animals. Previous studies have indicated that the pPVT is integral in the shifts in HPA responsiveness after repetitive homotypic stress in adults. The contribution of the pPVT to the distinctive hormonal response to homotypic stress demonstrated by prepubertal animals is presently unknown. Therefore, the hormonal response following homotypic stress will be assessed in prepubertal and adult animals that have had pPVT function disrupted through excitotoxic lesions. The successful completion of the experiments proposed in these Aims will establish the different ways in which the brains of prepubertal and adult animals respond to repeated stress, as well as begin to identify neural substrates that allow organisms at different stages of development to process stressful experiences differently. Furthermore, data from these experiments will provide myriad points of departure for future studies to assess how pubertal development and repeated exposure to stress shape neural pathways important in stress responsiveness and emotionality.
Pubertal development is marked by substantial changes in many hormonal systems. One such system is that which controls the hormones released during times of stress. Our long-term goal is to identify how pubertal development and stressful experiences interact to modulate this system and the impact of these interactions on physiological and neurobiological function.