Animal model of menopausal depressive-like state in female mice: prolongation of immobility time in the forced swimming test following ovariectomy

Rationale: The onset of menopause produces a depressive state in women, but the mechanism involved in menopause-induced depression is poorly understood. Objective: Building upon previous studies that used the duration of immobility in male rodents during the forced swimming test as a behavioral measure of the depression-like state, we investigated whether the duration of immobility in female mice was altered following bilateral ovariectomy. We also evaluated the chronic effects of estradiol, antidepressants, scopolamine, and diazepam on both the duration of immobility and uterine weight. Methods: We bilaterally resected the ovaries of ICR albino female mice at 9 weeks of age. The day after the surgery, drug treatment was started once per day for 2 weeks, after which, the behavioral test was administered. The duration of immobility was measured during the last 4 min of the 6-min trial. Results: Bilateral ovariectomy significantly increased the duration of immobility. Chronic treatment with estradiol (15-30 mu g kg(-1)day(-1) prevented the prolongation of immobility following ovariectomy and produced a significant increase in uterine weight. Chronic treatment with imipramine, fluvoxamine, and milnacipran at 5, 10, and 15 mg kg(-1) day(-1), respectively, significantly reduced the duration of immobility, whereas treatment with scopolamine or diazepam (0.5, 1.0, and 2.0 mg kg(-1) day(-1)for both) was ineffective. Conclusion: Based on these results, we suggest that the prolongation of immobility in female mice following ovariectomy may be a useful tool for investigating menopausal depression.