Estrada-Camarena Erika, Fernández-Guasti Alonso, López-Rubalcava Carolina
Subdirección de Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñíz, México City, DF, México.
Neuropsychopharmacology. 2006 Feb;31(2):247-55. doi: 10.1038/sj.npp.1300821.
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: 17beta-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 microg/rat) and EE(2) (5 microg/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 microg/rat) or EE(2) (1.25 microg/rat), was tested in the FST. The results showed that 8-OH-DPAT (0.25 and 0.5 mg/kg), E(2) (10 microg/rat), and EE(2) (5 microg/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).
本研究的目的是探讨5-羟色胺（5-HT）1A受体在两种雌激素化合物：17β-雌二醇（E₂）和乙炔雌二醇（EE₂）于强迫游泳试验（FST）中的抗抑郁样作用中可能发挥的作用。所有实验均使用去卵巢的雌性Wistar大鼠。作为阳性对照，单独分析了5-HT1A受体激动剂8-羟基-2-（二-n）-丙基-氨基四氢萘（8-OH-DPAT；0.0625、0.125、0.25和0.5mg/kg）或与WAY 100635（0.5和1.0mg/kg）联合使用在FST中的作用。为了分析5-HT1A受体在雌激素抗抑郁样作用中的参与情况，研究了选择性拮抗剂WAY 100635（0.5和1.0mg/kg）与E₂（10μg/只大鼠）和EE₂（5μg/只大鼠）联合使用在FST中的作用。在这种情况下，WAY 100635要么与雌激素同时给药（在FST试验前48小时），要么在FST前30分钟给药。另一方面，在FST中测试了次优剂量的8-OH-DPAT（0.0625mg/kg）与无效剂量的E₂（2.5μg/只大鼠）或EE₂（1.25μg/只大鼠）联合使用的情况。结果表明，8-OH-DPAT（0.25和0.5mg/kg）、E₂（10μg/只大鼠）和EE₂（5μg/只大鼠）自身均发挥了抗抑郁样作用。5-HT1A受体拮抗剂WAY 100635与8-OH-DPAT或E₂联合应用时，可阻断它们的抗抑郁样作用，但不能阻断EE₂诱导的抗抑郁样作用。有趣的是，当拮抗剂在FST前30分钟应用时，它能够消除EE₂对不动行为的作用，而对E₂的作用没有影响。最后，当次阈值剂量的8-OH-DPAT与无效剂量的E₂或EE₂联合使用时，观察到了抗抑郁样作用。这些结果支持了5-HT1A受体是E₂抗抑郁样作用的介导因子之一，并且可能间接促成EE₂诱导的抗抑郁样作用这一观点。
