Abstract

Studies show that women are at greater risk of developing stress related disorders such as depression or anxiety. It is also known that sex differences exist in the inflammatory response and that altered inflammatory signaling in the brain is involved in the development of affective disorders, possibly through its effect on neurotransmitter metabolism. This study analyzes changes in pro and anti-inflammatory cytokine expression and monoaminergic activity in the hippocampus, as well as changes in the HPA axis and behavior after exposure to chronic social instability stress in female mice. Results indicate increased HPA axis activity in stressed mice, manifested by higher plasma corticosterone levels and lower GR expression levels in the hypothalamus. No differences were found in hippocampal Il-6 and TNF-alpha proinflammatory cytokines, although a reduction was observed in IL-10 expression, accompanied by increased serotoninergic and noradrenergic activity. Stressed mice also showed a decrease in sucrose consumption, supporting the idea that in addition to proinflammatory cytokines, depressive behavior may also be influenced independently by the suppression of anti-inflammatory agents. Nevertheless, in the forced swimming test only was observed an increase in climbing behavior. This finding, alongside the increased noradrenergic and serotoninergic activity observed, may be indicative of anxiety. Data suggest that the social instability model may be useful to study different mechanisms involved in the development of stress-related psychopathologies in females.

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