Inflammatory Factors Mediate Vulnerability to a Social Stress-Induced Depressive-like Phenotype in Passive Coping Rats

Biol Psychiatry. 2015 Jul 1;78(1):38-48. doi: 10.1016/j.biopsych.2014.10.026. Epub 2014 Nov 25.


Background: Coping strategy impacts susceptibility to psychosocial stress. The locus coeruleus (LC) and dorsal raphe (DR) are monoamine nuclei implicated in stress-related disorders. Our goal was to identify genes in these nuclei that distinguish active and passive coping strategies in response to social stress.

Methods: Rats were exposed to repeated resident-intruder stress and coping strategy determined. Gene and protein expression in the LC and DR were determined by polymerase chain reaction array and enzyme-linked immunosorbent assay and compared between active and passive stress-coping and unstressed rats. The effect of daily interleukin (IL)-1 receptor antagonist before stress on anhedonia was also determined.

Results: Rats exhibited passive or active coping strategies based on a short latency (SL) or longer latency (LL) to assume a defeat posture, respectively. Stress differentially regulated 19 and 26 genes in the LC and DR of SL and LL rats, respectively, many of which encoded for inflammatory factors. Notably, Il-1β was increased in SL and decreased in LL rats in both the LC and DR. Protein changes were generally consistent with a proinflammatory response to stress in SL rats selectively. Stress produced anhedonia selectively in SL rats and this was prevented by IL-1 receptor antagonist, consistent with a role for IL-1β in stress vulnerability.

Conclusions: This study highlighted distinctions in gene expression related to coping strategy in response to social stress. Passive coping was associated with a bias toward proinflammatory processes, particularly IL-1β, whereas active coping and resistance to stress-related pathology was associated with suppression of inflammatory processes.

Keywords: Affective disorders; Coping; Inflammation; Interleukin 1β; Social defeat; Susceptibility.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Psychological / drug effects
  • Adaptation, Psychological / physiology*
  • Anhedonia / drug effects
  • Animals
  • Depression / etiology
  • Depression / genetics*
  • Depression / metabolism
  • Dominance-Subordination
  • Dorsal Raphe Nucleus / metabolism*
  • Gene Expression
  • Inflammation Mediators / metabolism*
  • Locus Coeruleus / metabolism*
  • Male
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Recombinant Proteins / pharmacology
  • Stress, Psychological / complications
  • Stress, Psychological / genetics*
  • Stress, Psychological / metabolism


  • Inflammation Mediators
  • Receptors, Interleukin-1
  • Recombinant Proteins