Estradiol valerate elicits antidepressant-like effects in middle-aged female rats under chronic mild stress

The purpose of this study was to analyze the antidepressant-like actions of estradiol valerate (1 or 2 mg/rat, single injection) or citalopram (5 or 10 mg/kg, chronically administered for 21 days) given independently or combined at low doses, to middle-aged ovariectomized female rats, as a model of human menopause. Animals were exposed to chronic mild stress, a model of depression that mimics anhedonia as revealed by diminished sucrose solution intake. Stressed rats decreased their sucrose preference 1 week after chronic stress and treatment with vehicle did not reverse this reduction. A single injection of estradiol valerate (2 mg/rat) produced an antidepressant-like action, evidenced as an increase in sucrose preference specific to stressed rats. Chronic citalopram (10 mg/kg) produced an antidepressant-like effect after 1 week. A single low-dose of estradiol valerate (1 mg/rat) did not potentiate or shorten the latency of action of chronic citalopram (5 mg/kg). These results reveal the antidepressant-like action of estrogens in middle-aged rats exposed to chronic stress. These data may be of importance for clinical depression in menopausal women.