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UBC Theses and Dissertations

Endocrine adaptation to repeated psychological stress in the adult male rat depends on central activation of vasopressin V1a receptors Gray, Jennifer Megan


The aim of this thesis was to investigate the brain pathways regulating the decline, or habituation of glucocorticoid responses to repeated exposure of psychological stress. In the first study, adult male rats were exposed to repeated bouts of restraint stress and tested for changes in endocrine responses and neuropeptide expression in the brain. Stress-induced elevations in glucocorticoids decreased as restraint was repeated, and this decline was associated with increased mRNA levels of the neuropeptide vasopressin in the medial amygdala and the bed nucleus of the stria terminalis. This suggested that central vasopressin signaling might be involved in coordinating glucocorticoid habituation. In a follow up experiment, adult male rats were again repeatedly restrained, however this time animals received continuous intracerebroventricular infusion of saline or an antagonist for the vasopressin V1a receptor. As expected, saline treated males showed stress-induced increases in vasopressin mRNA levels and habituation of glucocorticoid responses. Blocking activation of the vasopressin V1a receptor had no effect on basal or acute stress glucocorticoid levels. Antagonism did however attenuate habituation of glucocorticoid responses during subsequent restraint exposures. These findings indicated that habituation of endocrine stress responses depends on central vasopressin signaling. In the final set of experiments, saline and antagonist treated male rats were again repeatedly restrained, but this time brains were analyzed for changes in cellular activation using immunohistochemical detection of Fos protein. Antagonism had no effect on basal Fos expression, but blunted the habituation of repeated stress-induced Fos responses within the hypothalamus and select forebrain regions. Furthermore, a separate experiment revealed that repeated restraint induces region-specific changes in central V1a receptor binding levels which included decreases in the hippocampus, thalamus and central amygdala, but increases in the septum and bed nucleus of the stria terminalis. Overall, these studies show that habituation of glucocorticoid responses depends on central vasopressin V1a receptor signaling. The findings also suggest that stress-induced increases in V1a receptor binding within the bed nucleus and septum might be especially relevant in promoting habituation of glucocorticoid responses.

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