Voluntary exercise facilitates adaptation to repeated stress: Potential neurochemical mediators, effects of exercise duration and stressor intensity, and implications for health and well-being

The stark contrast in the effects of regular exercise and stress on a large number of physical and psychological health outcomes has compelled many investigators to propose that the health benefits of habitual physical activity may be mediated, at least in part, through an indirect effect of increased stress resistance. While the specific mechanisms by which such protection may be conferred remain to be elucidated, it has been hypothesized that the physiological effects of regular exercise may include or induce modifications in an organism's response to stress. Among a number of coordinated response systems that are activated by stress, the neuroendocrine hypothalamo-pituitary-adrenocortical (HPA) axis response, ultimately responsible for the secretion of glucocorticoid hormones (corticosterone [CORT] in rodents), serves as the primary focal point of this thesis, as dysregulation within this system has been specifically implicated in the mechanisms by which stress can negatively impact health. While previous studies have typically not reported reliable effects of voluntary physical activity on HPA axis responses to various acute stressor exposures, the potential for regular exercise to alter the way the body and brain respond under conditions of repeated stress remains largely unexplored. The work presented in this thesis first provides evidence that chronic voluntary wheel running reliably facilitated CORT response habituation to repeated audiogenic stress exposures relative to that exhibited by sedentary rats. Next, an analysis of the regulation of a targeted subset of neurochemical systems, at the level of gene transcription, possibly involved in mediating the facilitation of habituation to repeated audiogenic stress by voluntary exercise is presented. The subsequent chapter consists of a series of experiments designed to further characterize the conditions required for voluntary exercise-induced enhancement of HPA axis response habituation to be expressed, specifically with respect to the duration of running wheel access prior to repeated stress onset and/or the specific stimulus to which animals are repeatedly exposed. When viewed collectively, the results are suggestive of a novel means by which regular exercise lessens the negative impact of repeated stress on physical and psychological health, although the precise physiological explanation for this phenomenon remains to be determined.