Reduced hippocampal IL-10 expression, altered monoaminergic activity and anxiety and depressive-like behavior in female mice subjected to chronic social instability stress

Abstract

Evidence indicates that release of pro-inflammatory cytokines induced by social stress contributes to affective disorders. Additionally, there are known sex differences in both the stress response and the stressors that can elicit this response. In this regard, the chronic social instability (CSI) rodent model of stress appears to be the best fit for the social nature of females. This study analyzed the effects of CSI on female mouse behavior, hippocampal cytokine expression, tryptophan metabolism and monoaminergic activity. The activity of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes were also measured. Results showed a decrease in sucrose consumption in stressed subjects, indicative of anhedonic behavior and an increase in climbing activity in the forced swimming test (FST) and in whisking behavior, which have been associated with anxiety. Decreased interleukin-10 (IL-10) expression was found in the hippocampus of the stressed mice, while no differences in pro-inflammatory cytokine expression and tryptophan (TRYP), kynurenine (KYN) or 3-hydroxy kynurenine (3-HK) levels were found. Increased hippocampal serotoninergic and noradrenergic activity was observed in stressed mice. The higher plasma corticosterone and lower hypothalamic glucocorticoid receptor (GR) expression levels showed an increase in HPA activity after CSI. No differences were found in the plasma estradiol levels or the central estrogen receptors (ERα and ERβ) expression levels. These data indicate that the CSI stress-induced behavioral and physiological changes associated with anxiety and depressive disorders. Although additional studies are warranted, the results suggest an involvement of anti-inflammatory cytokines in the biobehavioral effects of social stress in female mice.