Participation of the 5-HT1A receptor in the antidepressant-like effect of estrogens in the forced swimming test

The aim of the present study was to explore the possible participation of the 5-HT1A receptor in the antidepressant-like action of two estrogenic compounds: 17 beta-estradiol (E-2) and ethynil-estradiol (EE2) in the FST. Ovariectomized female Wistar rats were used in all experiments. As a positive control, the effect of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n)- propil-aminotetraline (8-OH-DPAT; 0.0625, 0.125, 0.25 and 0.5 mg/kg) alone or in combination with WAY 100635 ( 0.5 and 1.0 mg/kg) was analyzed in the FST. In order to analyze the participation of the 5-HT1A receptor in the antidepressant-like actions of estrogens, the effect of the selective antagonist WAY 100635 (0.5 and 1.0 mg/kg) in combination with E-2 (10 mu g/rat) and EE2 (5 mu g/rat) was studied in the FST. In this case, WAY 100635 was administered either simultaneously with the estrogens ( 48 h before the FST test) or 30 min before the FST. On the other hand, a suboptimal dose of 8-OH-DPAT (0.0625 mg/kg), combined with a noneffective dose of E-2 (2.5 mu g/rat) or EE2 (1.25 mu g/rat), was tested in the FST. The results showed that 8-OH-DPAT (0.25 and 0.5 mg/kg), E-2 ( 10 mu g/rat), and EE2 (5 mu g/rat), by themselves, exerted an antidepressant-like action. The antagonist to the 5-HT1A receptor WAY 100635, when applied together with 8-OH-DPAT or E-2, blocked their antidepressant-like actions, but not the one induced by EE2. Interestingly, when the antagonist was applied 30 min before the FST, it was able to cancel the actions of EE2 on immobility behavior, and had no effect on the actions of E-2. Finally, when a subthreshold dose of 8-OH-DPAT was combined with a noneffective dose of either E-2 or EE2, an antidepressant-like action was observed. The results support the notion that the 5-HT1A receptor is one of the mediators of the antidepressant-like action of E-2, and could indirectly contribute to the one induced by EE2.