4.4 Article

Characterizing the behavioral and neuroendocrine features of susceptibility and resilience to social stress

Journal

NEUROBIOLOGY OF STRESS
Volume 17, Issue -, Pages -

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.ynstr.2022.100437

Keywords

Chronic social defeat stress; Coping behaviors; Threat discrimination; Social; Avoidance; Predictive traits

Categories

Funding

  1. Hope for Depression Research Foundation (HDRF)
  2. Pritzker Neuropsychiatric Disorders Research Consortium
  3. National Institute of Mental Health [R01MH104261]
  4. National Institute on Drug Abuse [U01DA043098]
  5. Office of Naval Research (ONR) [N00014-12-1-0366, N00014-19-1-2149]

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Evaluating and coping with stressful social events as they unfold is crucial for overcoming them without long-lasting detrimental effects. This study focuses on characterizing the behavioral, physiological, and neuroendocrine profiles of mice before, during, and after Chronic Social Defeat Stress (CSDS). The findings suggest that early coping mechanisms during the initial social stress encounter better predict whether mice will become resilient or susceptible to social stress.
Evaluating and coping with stressful social events as they unfold is a critical strategy in overcoming them without long-lasting detrimental effects. Individuals display a wide range of responses to stress, which can manifest in a variety of outcomes for the brain as well as subsequent behavior. Chronic Social Defeat Stress (CSDS) in mice has been widely used to model individual variation following a social stressor. Following a course of repeated intermittent psychological and physical stress, mice diverge into separate populations of social reactivity: resilient (socially interactive) and susceptible (socially avoidant) animals. A rich body of work reveals distinct neurobiological and behavioral consequences of this experience that map onto the resilient and susceptible groups. However, the range of factors that emerge over the course of defeat have not been fully described. Therefore, in the current study, we focused on characterizing behavioral, physiological, and neuroendocrine profiles of mice in three separate phases: before, during, and following CSDS. We found that following CSDS, traditional read-outs of anxiety-like and depression-like behaviors do not map on to the resilient and susceptible groups. By contrast, behavioral coping strategies used during the initial social stress encounter better predict which mice will eventually become resilient or susceptible. In particular, mice that will emerge as susceptible display greater escape behavior on Day 1 of social defeat than those that will emerge as resilient, indicating early differences in coping mechanisms used between the two groups. We further show that the social avoidance phenotype in susceptible mice is specific to the aggressor strain and does not generalize to conspecifics or other strains, indicating that there may be features of threat discrimination that are specific to the susceptible mice. Our findings suggest that there are costs and benefits to both the resilient and susceptible outcomes, reflected in their ability to cope and adapt to the social stressor.

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