Interaction between estrogens and antidepressants in the forced swimming test in rats

Rationale. Several reports suggest that estrogens possess antidepressant effects and could facilitate the action of some antidepressants. Objective. To analyze the interaction between three different types of estrogens, 17beta-estradiol (E-2), ethinylestradiol (EE2) or diethyl-stilbestrol (DES) and the antidepressants, fluoxetine (FLX) or desipramine (DMI) in ovariectomized female rats subjected to an animal model for the study of antidepressant compounds, the forced swimming test (FST). Methods. The effect of the combination of a sub-optimal dose of FLX (2.5 mg/kg) or DMI (2.5 mg/kg) with a sub-active dose of E-2 (10 mug/kg), EE2, (2.5 or 5 mug/kg) or DES (1 mg/kg) was analyzed in both the FST and the open field paradigm. Results. The combination of a sub-optimal dose of E-2 or DES with that of the antidepressant DMI resulted in a clear antidepressant-like effect, evidenced by a significant decrease in immobility accompanied by an increase in climbing behavior. Sub-optimal doses of either E-2 or DES also facilitated the antidepressant-like effect of a sub-optimal dose of FLX. In this case, a decrease in immobility with a concomitant increase in swimming behavior was observed. Finally, the combination of EE2 with either DMI or FLX decreased immobility and induced an increase in both swimming and climbing behaviors. All combinations decreased rats' locomotor activity when evaluated in the open field test. Conclusion. In the FST estrogens were able to facilitate the action of two different kinds of antidepressants; however, these effects were dependent on the type of estrogen used.