Modeling vicarious social defeat stress in rodents for investigating emotional stress-induced depression

Vicarious trauma, a form of emotional stress experienced by observing the suffering of others has gained prominence as a major contributor to depression and other stress-related disorders. Traditional animal models of depression such as Chronic Social Defeat Stress (CSDS) focus on physical stressors but fail to replicate the psychological dimensions of vicarious trauma. The Vicarious Social Defeat Stress (VSDS) model fills this gap by inducing emotional stress without physical injury. This enables us to investigate the neural, behavioral and molecular mechanisms unique to emotional stress-induced depression. Studies have shown differential pharmacological efficacy of antidepressants in emotional versus physical stress, emphasizing the necessity of models like VSDS to investigate these variations comprehensively. This review integrates insights from VSDS studies focusing on dysregulations in the hypothalamic pituitary adrenal (HPA) axis, neuroendocrine modalities, neuroinflammatory processes mediated by IL-6, IL-1β and CRH-BDNF signaling. We explore diverse behavioral strategies for VSDS modeling, emphasizing its utility in capturing the complex neurobiological and behavioral outcomes of vicarious stress. Sex-specific differences in vicarious stress have also been investigated. Additionally, we address limitations of current models, specifically their male-centric design and propose future directions, including the development of female-specific paradigms and enhancing ecological validity. By integrating insights into behavioral outcomes, sex differences, resilience and susceptibility, this review positions VSDS as a crucial model for enhancing our understanding of emotional stress and its implications in neuropsychiatric disorders.