Protective effects of resveratrol on social stress‐induced neuroinflammation and depressive‐like behavior

Abstract

Social stress precipitates psychiatric disorders, however only a subset of the population is susceptible. This may result from differences in coping strategy and sequent inflammation. Using a resident-intruder paradigm in rats, we previously identified two distinct phenotypic responses to stress. Active coping (AC) rats spent more time resisting in upright postures in the presence of a dominant resident rat than did passive coping (PC) rats. PC rats developed behavioral, inflammatory and neuroendocrine endpoints comparable to depression, while AC rats did not. The present study determined if resveratrol (RSV, 10mg/kg/day), a natural anti-inflammatory, could protect against stress-induced neuroinflammation and produce antidepressant-like effects in socially defeated rats (stress vs control 30min/day for 5 days). In PC rats, proinflammatory proteins (IL-1β, IL-6, GM-CSF) were elevated 5 days after the final social defeat within the locus coeruleus, a noradrenergic brain region implicated in depression. Alternitavely, in AC rats, certain proinflammatory cytokines were decreased (INF-ϒ and MCP-1). Flow cytometry revealed increased splenic inflammatory proteins in PC as compared to AC and controls. Elevated inflammation in the PC phenotype was also related to anhedonia in the sucrose preference test. Notably, RSV blocked the inflammation produced by social defeat and inhibited the development of depressive-like behavior. These data confirm that the depressive-like phenotype evident in PC rats may be driven by stress-induced inflammation as evidenced by anti-depressant-like effects of RSV. 5P20GM103641