Cardiometabolic and anxiogenic consequences of chronic social defeat stress in male mice

Abstract

Social adversity, such as that which occurs during subjugation to a lower social status, has profound psychological and cardiometabolic consequences that are conserved across species. Clinically, such adversity often arises from being of a lower socioeconomic status and may contribute to health disparities in cardiometabolic and affective disorders. To develop a better understanding of the cardiometabolic consequences of social adversity, we employ chronic social defeat stress (CSDS) in adult male mice. CSDS results in increases in body mass, that are accompanied by elevated lean and fluid mass, as well as several somatic indices of chronic stress. Moreover, mice exposed to CSDS exhibit increased anxiety-like behavior, spending more time in the closed arms of the elevated plus maze and less time in the center of an open field arena. Regarding cardiovascular parameters, initial social defeat sessions result in increases in blood pressure, activity, and temperature in comparison with control mice. Interestingly, while blood pressure returns to basal levels by the start of the light cycle for the first few days of defeat, 14 days of CSDS results in sustained elevations in blood pressure, lower activity and lower body temperature. Finally, the results of heart rate variability, spontaneous baroreflex sensitivity and adrenal transcriptome analyses were consistent with CSDS-induced autonomic dysfunction, effects that may contribute to the hypertension observed. Collectively, these data suggest that CSDS may be useful for modeling hypertension induced by chronic social stress, thereby enabling us to better understand the mechanisms that contribute to stress-induced cardiometabolic disease.