Peripheral and central effects of repeated social defeat stress: Monocyte trafficking, microglial activation, and anxiety

B. F. Reader, B. L. Jarrett, D. B. McKim, E. S. Wohleb, J. P. Godbout, J. F. Sheridan

Research output: Contribution to journalReview articlepeer-review


The development and exacerbation of depression and anxiety are associated with exposure to repeated psychosocial stress. Stress is known to affect the bidirectional communication between the nervous and immune systems leading to elevated levels of stress mediators including glucocorticoids (GCs) and catecholamines and increased trafficking of proinflammatory immune cells. Animal models, like the repeated social defeat (RSD) paradigm, were developed to explore this connection between stress and affective disorders. RSD induces activation of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis activation, increases bone marrow production and egress of primed, GC-insensitive monocytes, and stimulates the trafficking of these cells to tissues including the spleen, lung, and brain. Recently, the observation that these monocytes have the ability to traffic to the brain perivascular spaces and parenchyma have provided mechanisms by which these peripheral cells may contribute to the prolonged anxiety-like behavior associated with RSD. The data that have been amassed from the RSD paradigm and others recapitulate many of the behavioral and immunological phenotypes associated with human anxiety disorders and may serve to elucidate potential avenues of treatment for these disorders. Here, we will discuss novel and key data that will present an overview of the neuroendocrine, immunological and behavioral responses to social stressors.

Original languageEnglish (US)
Pages (from-to)429-442
Number of pages14
StatePublished - Mar 9 2015
Externally publishedYes


  • Anxiety-like behavior
  • Cell trafficking
  • Inflammation
  • Macrophages
  • Microglia
  • Repeated social defeat

ASJC Scopus subject areas

  • General Neuroscience


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