Gene and protein expression in a rodent model of social stress: Implications for depression‐cardiovascular disease comorbidity

Abstract

Psychosocial stress is linked to psychiatric disorders (eg, depression) and comorbid cardiovascular disease, but underlying mechanisms remain unknown. We previously identified two distinct phenotypic responses to social stress in rats (resident‐intruder model). One population exhibited passive behaviors, assuming a defeat posture within a short latency (SL, <300s). The other exhibited proactive behaviors and a longer latency (LL, >;300s). The SL phenotype was associated with endocrine and behavioral characteristics resembling depression and heart rate variability alterations indicating greater cardiovascular disease risk. As the locus coeruleus (LC) and dorsal raphe (DR) are implicated in the pathogenesis of depression, this study hybridized RNA from the LC or DR (n=4–6/group) to RT2 Profiler PCR arrays (SABiosciences) to identify expression of 88 genes involved in GPCR signaling. 22 genes (13 up, 9 down) in LC and 20 genes (11 up, 9 down) in DR were differentially expressed in SL vs LL rats (>;1.5 fold), many involved in inflammation. Elisa analysis confirmed stress‐induced suppression of brain Il1β and MCP‐1 in LL rats and increased Il1β in SL rats. These data suggest distinct stress‐induced adaptations in inflammatory markers may underlie susceptibility to a depressive phenotype and offers targets that may impact depression‐cardiovascular disease comorbidity. MH058250, MH040008, NARSAD‐17830