Protective effect of metformin against ovariectomy induced depressive- and anxiety-like behaviours in rats: role of oxidative stress

Abstract

Several studies have shown that low estrogen levels can lead to an increase in the incidence of depression and anxiety during menopause. The hippocampus and prefrontal cortex are parts of the brain involved in depressive- and anxiety-like behaviors. Recent studies have revealed that metformin has neuroprotective effects mainly due to its antioxidant properties. The aim of the present study was to examine the therapeutic potential of metformin in depressive- and anxiety-like behavior as well as oxidative stress in the prefrontal cortex and hippocampus of ovariectomized rats. Young female Wistar Albino rats were distributed into four groups (n:8): control, metformin-administered control, ovariectomized and metformin administered ovariectomized groups. Metformin (25 mg/kg) was administered daily by oral gavage for 2 weeks. Forced swimming test and open field test were performed to evaluate depression- and anxiety-like behaviors, respectively. Following the treatment with metformin, the tissues of the hippocampus and prefrontal cortex were isolated for the measurement of malondialdehyde, reduced glutathione and ascorbic acid contents. Ovariectomy resulted in depressive- and anxiety-like behaviors, and besides, increased content of malondialdehyde in both prefrontal cortex and hippocampus. The levels of ascorbic acid and glutathione were found to be reduced in ovariectomized rats. Metformin treatment significantly decreased depressive behaviour and malondialdehyde content in the prefrontal cortex. Reducing oxidative stress of the prefrontal cortex was suggested as a possible mechanism implicated in the beneficial effects of metformin on ovariectomy-induced depressive-like behaviour. We believe that the therapeutic efficiency of metformin needs to be tested for potential clinical use in surgical menopause or gonadal hormone deficiency women with depression.