Not just a witness: Highlighting the utility of witness social defeat stress for the examination of neuroimmune-cardiovascular interactions across diverse populations

Exposure to stress has widespread pathological consequences in terms of neuropsychiatric disorders and cardiovascular disease. Psychosocial stressors represent the most highly impactful and commonly experienced form of stress and, in preclinical studies, have been found to induce distinct overlapping immune and cardiovascular alterations. Historically, the social defeat model has been fundamental in providing insights into the autonomic and neuroimmune mediators of cardiovascular dysfunction in the face of social stress exposure. However, this procedure relies on aggressive, physical interaction between rodents and is limited by its almost exclusive application to young adult males. This challenges the possibility of using social defeat to generate data in rodents that can be translated into social stress-related processes in both men and women across the lifespan. More recently, a novel vicarious social defeat procedure has been developed, wherein a rodent bears witness to an aggressive social defeat encounter between two males from the safety of an adjacent compartment. This review first discusses the existing data regarding stress-induced cardiovascular alterations and the underlying autonomic and neuroimmune mediators of social defeat while critically discussing the limitations of this model. New prospects are then offered based on recent findings across a diverse population of rodent species, sexes, and ages to support the use of vicarious/witness social defeat model as an optimal strategy to investigate social stress-related autonomic, neuroimmune, and cardiovascular processes using more comprehensive and inclusive methods.