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

• Published in: Biological psychiatry (1969) Vol. 78; no. 1; pp. 38 - 48
• Main Authors: Wood, Susan K, Wood, Christopher S, Lombard, Calliandra M, Lee, Catherine S, Zhang, Xiao-Yan, Finnell, Julie E, Valentino, Rita J
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2015
• Subjects: Adaptation, Psychological - drug effects; Adaptation, Psychological - physiology; Affective disorders; Anhedonia - drug effects; Animals; Coping; Depression - etiology; Depression - genetics; Depression - metabolism; Dominance-Subordination; Dorsal Raphe Nucleus - metabolism; Gene Expression; Inflammation; Inflammation Mediators - metabolism; Interleukin 1β; Locus Coeruleus - metabolism; Male; Psychiatry; Rats; Rats, Long-Evans; Rats, Sprague-Dawley; Receptors, Interleukin-1 - antagonists & inhibitors; Recombinant Proteins - pharmacology; Social defeat; Stress, Psychological - complications; Stress, Psychological - genetics; Stress, Psychological - metabolism; Susceptibility; Interleukin 1β; Inflammation; Coping; Affective disorders; Social defeat; Susceptibility
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2014.10.026

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.