Long-term ovariectomy enhances anxiety and depressive-like behaviors in mice submitted to chronic unpredictable stress

Ovarian hormones exert anti-depressive and anxiolytic actions. In this study we have analyzed the effects of ovariectomy on the development of anxiety and depression-like behaviors and on cell proliferation in the hippocampus of mice submitted to chronic unpredictable stress. Animals submitted to stress 4 months after ovariectomy showed a significant increase in immobility behavior in the forced swimming test compared to animals submitted to stress 2 weeks after ovariectomy. In addition, long-term ovariectomy resulted in a significant decrease on the time spent in the open arms in the elevated plus-maze test compared to control animals. Stress did not significantly affect cell proliferation in the hilus of the dentate gyrus. However, ovariectomy resulted in a significant decrease in cell proliferation. These results indicate that long-term deprivation of ovarian hormones enhances the effect of chronic unpredictable stress on depressive- and anxiety-like behaviors in mice. Therefore, a prolonged deprivation of ovarian hormones may represent a risk factor for the development of depressive and anxiety symptoms after the exposure to stressful experiences.

Research highlight
► The effects of ovariectomy on the development of anxiety and depression-like behaviors and on cell proliferation in the hippocampus of mice submitted to chronic unpredictable stress has been analyzed.
► Animals submitted to stress 4 months after ovariectomy showed a significant increase in immobility behavior in the forced swimming test compared to animals submitted to stress 2 weeks after ovariectomy.
► Long-term ovariectomy resulted in a significant decrease on the time spent in the open arms in the elevated plus-maze test compared to control animals.
► Ovariectomy resulted in a significant decrease in cell proliferation in the dentate gyrus.
► These results suggest that a prolonged deprivation of ovarian hormones may represent a risk factor for the development of depressive and anxiety symptoms after the exposure to stressful experiences.