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The present study evaluated the possible antidepressant-like action of the natural estrogen 17beta-estradiol (E(2), 2.5-10 microg/rat), the synthetic steroidal estrogen ethinyl-estradiol (EE(2), 1.25-10.0 microg/rat), and the nonsteroidal synthetic estrogen, diethyl-stilbestrol (DES, 0.25-1.0 mg/rat) in ovariectomized adult female Wistar rats using the forced swimming test (FST). The behavioral profile induced by the estrogens was compared with that induced by the antidepressants fluoxetine (FLX, 2.5-10 mg/kg) and desipramine (DMI, 2.5-10 mg/kg). In addition, the temporal course of the antidepressant-like action of the estrogenic compounds was analyzed. FLX and DMI induced an antidepressant-like effect characterized by a reduced immobility and increased swimming for FLX and decreased immobility and increased climbing for DMI. Both E(2) and EE(2) produced a decrease in immobility and an increase in swimming, suggesting an antidepressant-like action. DES did not affect the responses in this animal model of depression at any dose tested. The time course analysis of the actions of E(2) (10 microg/rat) and EE(2) (5 microg/rat) showed that both compounds induced an antidepressant-like effect observed 1 h after their injection lasting for 2-3 days.

Antidepressant-Like Effect of Different Estrogenic Compounds in the Forced Swimming Test