title: Inflammatory Factors Mediate Vulnerability to a Social Stress-Induced Depressive-like Phenotype in Passive Coping Rats.
abstract: 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.
authors: Department of Anesthesiology, Division of Stress Neurobiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, South Carolina. Electronic address: susan.wood@uscmed.sc.edu.
authors: Susan K
authors: SK
authors: Wood
authors: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, South Carolina.
authors: Christopher S
authors: CS
authors: Wood
authors: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, South Carolina.
authors: Calliandra M
authors: CM
authors: Lombard
authors: Department of Anesthesiology, Division of Stress Neurobiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors: Catherine S
authors: CS
authors: Lee
authors: Department of Anesthesiology, Division of Stress Neurobiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors: Xiao-Yan
authors: XY
authors: Zhang
authors: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, South Carolina.
authors: Julie E
authors: JE
authors: Finnell
authors: Department of Anesthesiology, Division of Stress Neurobiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors: Rita J
authors: RJ
authors: Valentino
mesh_terms: D000223:Adaptation, Psychological / Q000187:drug effects / Q000502:physiology*; D059445:Anhedonia / Q000187:drug effects; D000818:Animals; D003863:Depression / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D004291:Dominance-Subordination; D065847:Dorsal Raphe Nucleus / Q000378:metabolism*; D015870:Gene Expression; D018836:Inflammation Mediators / Q000378:metabolism*; D008125:Locus Coeruleus / Q000378:metabolism*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D013315:Stress, Psychological / Q000150:complications / Q000235:genetics* / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins
keywords: Affective disorders; Coping; Inflammation; Interleukin 1β; Social defeat; Susceptibility