Grant: Operating Grant

The hypothalamic-pituitary-adrenal (HPA) axis is a hormonal system that regulates glucocorticoid steroid secretion that is essential for maintaining physiological balance in the face of real or perceived threats to the body (i.e. stress). Glucocorticoid hypersecretion, however, has been implicated in the development of mood disorders, including anxiety and depression. Thus, the HPA axis must be both tightly regulated and equally responsive to the demands of stress. Studies in humans and rodents have shown that when exposure to the same stimulus is repeated in a predictable manner, the magnitude of the glucocorticoid response can decline or habituate to successive stimulus exposures. Moreover, impaired HPA axis habituation and maladaptive behavioral coping styles have been proposed as leading causes for mood disorders in humans. Converging data from our rodent models suggest that stress habituation is met by an increase in the activity of AVP-containing pathways and V1A receptors in the brain. Thus, rats bearing central injections of a V1A receptor antagonist fail to show a decline in glucocorticoid secretion during repeated stress. This finding may be linked to changes in testosterone secretion during different times of the lifespan. We found that animals robbed of testosterone exposure at birth, as well as in adulthood, express a lower capacity for HPA axis habituation. We also have evidence to show that coping styles are positively correlated with AVP expression in brain regions known to regulate behavioral and hormonal responses to stress. We hypothesize that changes in central AVP and V1A receptor function play a critical role in stress adaptation. Experiments are proposed to make novel inroads on these mechanisms, certain to increase our understanding why some individuals are vulnerable to stress.