Neuroendocrine Effects of Repeated Social Defeat

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Chronic or repeated exposure to stress produces plasticity in a number of neural systems, including those that regulate the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis has widespread effects on physiology and behavior, including modulation of metabolism and cardiovascular function. Changes in basal activity as well as subsequent stress-induced HPA activity are seen in animals exposed to repeated stress such as cold or restraint. This project uses a more naturalistic model of stress in rodents, that of repeated exposure to social defeat. Defeat in the context of social environment, including which individual is a resident or an intruder in the local area, is a familiar situation in the natural life of many social rodents such as rats. Although a single defeat produces neuroendocrine and behavioral effects that last a few weeks, it is more common in the wild to have an individual animal regularly subjected to defeat. Therefore, repeated defeat in rats represents a potentially powerful model for the study of neural plasticity associated with chronic, repeated stress. Using a novel combination of molecular biology and behavior, the goals of this project are to 1) characterize how basal and stress-induced HPA activity change in rats subject to repeated defeat; 2) study the specific role of the paraventricular thalamus, a brain region that inhibits HPA responses in other stress situations, in the repeated defeat paradigm; and 3) identify novel brain regions in which activity is increased by repeated defeat, since these are potential sites of regulation of HPA activity. Results will be important for identifying novel brain circuitry involved in the modulation of behavior, and with an impact on our understanding more about the role of social versus physical stress, and about the evolution of sociality. This project also fosters the career of a new investigator who combines an unusual background in molecular biology and behavior.