Venlafaxine reduces the striatal il6/il10 ratio and increases hippocampal GR expression in female mice subjected to chronic social instability stress.

Women are twice as likely as men to develop depression and antidepressant treatment is more frequent in females. Moreover, neuroinflammatory changes related to affective disorders differ in accordance with sex. Despite this evidence, female populations have been largely omitted from preclinical experiments studying antidepressants. The aim of this work is to analyze the potential restorative effect of venlafaxine on an animal model of depression. Female CD1 mice were subjected to chronic social instability (CSI) stress for 7 weeks, and were administered venlafaxine during the last 3 weeks of the stress period. Behavioral and physiological parameters were then analyzed. Stressed mice showed a decreased sucrose preference and increased whisking behavior, and had a lower body weight, higher plasma corticosterone levels and increased hypothalamic GR expression. They also had lower levels of 5-HT, 5-HIAA and NA and a higher KYN/TRYP ratio in the hippocampus. Moreover, CSI increased striatal IL-6 mRNA expression levels. Venlafaxine treatment reduced the striatal IL-6/IL-10 ratio and increased hippocampal GR expression, although it did not reverse stress-induced behavioral changes. In conclusion, seven weeks of exposure to CSI produced depressive-like alterations in female mice. The venlafaxine treatment regimen was found to have a modest anti-inflammatory effect in the striatum and increased hippocampal GR mRNA, although it failed to redress stress-induced behavioral disturbances.