Physiology Division, Preclinical Sciences, Faculty of Medicine, Thammasat University, Pathumthani 12120, Thailand.
Pharmacol Biochem Behav. 2011 Jun;98(4):503-10. doi: 10.1016/j.pbb.2011.02.023. Epub 2011 Mar 5.
The anxiolytic effect of fluoxetine (Flx) was often ineffective in postmenopausal and estrogen-deficient patients, but such effect had not been experimentally demonstrated, particularly in the female rat model of estrogen deficiency. Here we determined the anxiety-like behaviors in ovariectomized (Ovx) rats treated for 4weeks with 10μg/kg 17β-estradiol s.c. (Ovx+E2), 10mg/kg Flx p.o. (Ovx+Flx) or a combination of both (Ovx+E2+Flx). Since Flx is known to induce anxiolysis in males, we first evaluated the Flx regimen in male rats. The results showed that anxiety-like behaviors were reduced in Flx-treated male rats. In contrast, Ovx+Flx rats still exhibited the same anxiety-like behaviors as in Ovx rats. Both Ovx+E2 and Ovx+E2+Flx rats, however, showed comparable reductions in anxiety-like behaviors, suggesting that Flx had no anxiolytic-like effect. Furthermore, E2 and E2+Flx similarly upregulated the mRNA expression of serotonin reuptake transporter (SERT) and tryptophan hydroxylase-2 in the dorsal raphé of Ovx rats, while having no effect on SERT expression in the frontal cortex, hippocampus, septum, amygdala and periaqueductal gray. In conclusion, Flx induced anxiolytic-like action in male rats. In Ovx rats, it was E2 and not Flx that exerted the anxiolytic-like action, which was mediated, in part, by altering serotonin metabolism in the dorsal raphé.
氟西汀（Flx）的抗焦虑作用在绝经后和雌激素缺乏的患者中常常无效，但这种作用尚未在实验中得到证实，特别是在雌激素缺乏的雌性大鼠模型中。在这里，我们确定了经过 4 周皮下注射 17β-雌二醇（Ovx+E2）、口服 10mg/kg Flx（Ovx+Flx）或两者联合治疗（Ovx+E2+Flx）的去卵巢（Ovx）大鼠的焦虑样行为。由于已知 Flx 可诱导雄性大鼠产生抗焦虑作用，我们首先评估了 Flx 方案在雄性大鼠中的作用。结果表明，Flx 治疗的雄性大鼠的焦虑样行为减少。相比之下，Ovx+Flx 大鼠仍表现出与 Ovx 大鼠相同的焦虑样行为。然而，Ovx+E2 和 Ovx+E2+Flx 大鼠均表现出相似的焦虑样行为减少，表明 Flx 没有抗焦虑样作用。此外，E2 和 E2+Flx 同样上调了去卵巢大鼠背中缝的 5-羟色胺再摄取转运体（SERT）和色氨酸羟化酶-2 的 mRNA 表达，而对额皮质、海马、隔核、杏仁核和中脑导水管周围灰质中的 SERT 表达没有影响。总之，Flx 在雄性大鼠中诱导出抗焦虑样作用。在去卵巢大鼠中，是 E2 而不是 Flx 发挥了抗焦虑样作用，这部分是通过改变背中缝的 5-羟色胺代谢来介导的。
