Long-term ovariectomy increases anxiety- and despair-like behaviors associated with lower Fos immunoreactivity in the lateral septal nucleus in rats

Abstract

In woman, surgical menopause is associated with anxiety and depression symptoms. Ovariectomy in rats has been proposed as an experimental model of surgical menopause, but its long-term effects on anxiety- and depression-like behaviors and relationship with cellular changes in specific brain structures are unknown. The effects of ovariectomy on anxiety- and despair-like behavior 1, 3, 6, 9, 12, and 15-weeks postovariectomy were evaluated. Fos-immunoreactivity was evaluated in the lateral septal nucleus (LSN). The effects were compared with rats in the proestrus-estrus and metestrus-diestrus phases of the ovarian cycle and with ovariectomized rats that received 17β-estradiol (OVXE). Three weeks postovariectomy, the rats exhibited an increase in anxiety-like behavior compared with PE and OVXE groups. Decreases in the locomotor activity and time spent grooming and rearing were detected in all the ovariectomized rats. In the forced swim test, the rats exhibited an increase in immobility time 6-weeks postovariectomy compared with control groups. The Fos-immunoreactivity in the LSN was significantly lower in all groups of ovariectomized rats compared with control groups. These findings indicate that rats develop anxiety-like behavior 3-weeks postovariectomy. Six weeks postovariectomy, the rats also developed despair-like behavior, which was associated with a reduction of Fos immunoreactivity in the LSN. Long-term ovariectomy may be considered a useful tool for understanding the development of neurobiological changes associated with surgical menopause. This model may also be useful for evaluating potential anxiolytic and antidepressant effects of diverse substances to ameliorate typical emotional and affective disorders during surgical menopause in women.