Cardiovascular and behavioral sequelae of witnessing social defeat stress in male and female rats

It is well recognized that exposure to social stress can contribute to psychosocial disorders (ie., depression) and comorbid medical disorders such as cardiovascular disease. While animal models of social defeat stress traditionally utilize a physical confrontation, recent studies have indicated that the psychological stress of witnessing the stressful event has long lasting behavioral consequences. In the present study we used the resident‐intruder paradigm to contrast the depressive‐like and cardiovascular consequences of social defeat stress in male Sprague Dawley rats that were directly exposed to the aggressive resident (intruder) with either male or female rats that were present in the cage, but only observing the stressful event (witness). Rats were implanted with cardiovascular transmitters that allowed for simultaneous measurements of blood pressure and ECG in two rats within the same cage (Data Sciences Intl). Following surgical recovery, rats were assigned to one of three groups; control, 5 consecutive days of social defeat (intruder, male), or observation of social defeat (witness, male or female) for 15 mins/day. For all experimental groups, cardiovascular telemetry was collected 24 hrs/day and continuous recordings were collected on the 1 st and 5 th exposure to stress/control. Five days after the final stress exposure all experimental rats were also subjected to the sucrose preference test to assess stress‐induced anhedonia. In agreement with our previous findings, social defeat stress produced a robust tachycardic and pressor response. Interestingly, the magnitude of increased blood pressure (MAP) and heart rate (HR) over controls was comparable between intruder and male witness rats. However, 12 hr light/dark cycle measurements revealed significantly greater increases in resting HR and MAP in male witness rats compared with controls and intruders. Female witness rats, on the other hand, exhibited blunted cardiovascular responsivity to social stress exposure compared with males and showed no long‐lasting changes in resting HR and MAP that was displayed in male witnesses. Importantly, assessment of depressive‐like behaviors using the sucrose preference test revealed that male witness rats displayed exaggerated anhedonia compared with male intruder rats while females again appeared unaffected. Taken together, these findings reveal that although females were generally unaffected by witnessing social defeat stress, in males, witnessing this social stressor may have a greater impact on the cardiovascular system and resulting depressive‐like behavior compared with experiencing the direct physical contact of social defeat stress. Support or Funding Information Research supported by 15SDG22430017 and P20GM103641.