Participation of the 5-HT1A Receptor in the Antidepressant-Like Effect of Estrogens in the Forced Swimming Test

Abstract

The aim of the present study was to explore the possible participation of the 5-HT 1A receptor in the antidepressant-like action of two estrogenic compounds: 17b-estradiol (E 2 ) and ethynil-estradiol (EE 2 ) in the FST. Ovariectomized female Wistar rats were used in all experiments. As a positive control, the effect of the 5-HT 1A 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-HT 1A 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 mg/rat) and EE 2 (5 mg/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 mg/rat) or EE 2 (1.25 mg/rat), was tested in the FST. The results showed that 8-OH-DPAT (0.25 and 0.5 mg/kg), E 2 (10 mg/rat), and EE 2 (5 mg/rat), by themselves, exerted an antidepressant-like action. The antagonist to the 5-HT 1A receptor WAY 100635, when applied together with 8-OH-DPAT or E 2 , blocked their antidepressant-like actions, but not the one induced by EE 2 . Interestingly, when the antagonist was applied 30 min before the FST, it was able to cancel the actions of EE 2 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 EE 2 , an antidepressant-like action was observed. The results support the notion that the 5-HT 1A receptor is one of the mediators of the antidepressant-like action of E 2 , and could indirectly contribute to the one induced by EE 2 .

Participation of the Monoaminergic System in the Antidepressant-Like Actions of Estrogens: A Review in Preclinical Studies

“…Furtheremore, the antidepressant-like actions of E2 and EE2, alone or in combination with fluoxetine require the activation of 5-HT1A receptors, since the selective 5-HT1A antagonist, WAY100635 blocked the antidepressantlike effect induced by these estrogens (Estrada-Camarena et al, 2006a;Estrada-Camarena et al, 2006b). In support of this proposal, the administration of the specific 5-HT1A postsynaptic receptor antagonist MM-77, canceled E2 antidepressant-like effects in the FST (López-Rubalcava et al, 2005).…”

Factors producing a menopausal depressive-like state in mice following ovariectomy

“…A recent study on ovariectomized rats (3 weeks after ovariectomy) revealed that the administration of 8-OH-DPAT (0.25 and 0.5 mg kg −1 ) at 60 min before the second trial significantly reduced the immobility count in the FST using a time-sampling technique (Estrada-Camarena et al 2006); however, this study did not compare ovariectomized rats with nonoperated or sham-operated controls. Owing to methodological differences in measuring immobility and the lack of a dose-dependent effect on the immobility count, it is difficult to explain the difference in the effect of 8-OH-DPAT between our results in mice and theirs in rats.…”

Anti-depressant effect of hesperidin in diabetic rats

“…The FST was designed as described by Porsolt et al (1978) and modified by Cryan et al (2002aCryan et al ( , 2002b and Estrada-Camarena et al (2006). A vertical plexiglas cylinder, 46 cm high and 20 cm wide was filled with tap water (23-25°C) to a depth of 30 cm, so that rats could not support themselves by touching the bottom with their paws or tail.…”