Walf Alicia A, Paris Jason J, Frye Cheryl A
Department of Psychology, The University at Albany-SUNY, 1400 Washington Avenue, Life Sciences Research 1058, Albany, NY 12222, USA.
Psychoneuroendocrinology. 2009 Jul;34(6):909-16. doi: 10.1016/j.psyneuen.2009.01.004. Epub 2009 Feb 11.
Decline in the ovarian steroid, estradiol (E(2)), with the menopause transition may influence cognitive and affective processing of older women and there is evidence that hormone replacement therapies (HRTs) with E(2)-mimetics may provide benefit in some, but not all, women. The parameters that play a role in determining whether the response to HRTs is positive are of interest. It may be that the likelihood for positive responses is related to the timing of E(2)-replacement following E(2) decline. As such, in the present study an animal model was utilized to investigate this. We investigated the effects of long- versus short-term E(2)-replacement by examining cognitive (object placement task), anxiety (open field, mirror maze, light-dark transition task), and depression (forced swim task) behavior of female rats that were ovariectomized (OVX) at middle-age (14 months) or older (19 months) and implanted with E(2)-filled implants at the time of surgery or after a delay of 5 months, or OVX at 14 months of age and never replaced with E(2). Rats were tested at 20 months of age. The hypothesis that was tested was that rats would have reduced anxiety and depression behavior and improved cognitive performance with E(2)-replacement at ovarian cessation, compared to a delay in E(2)-replacement. Performance in the object placement task was improved in rats that were OVX and then received continuous E(2)-replacement, compared to those that were OVX and continuously administered placebo vehicle. In the open field and forced swim task, there was an increase in anti-anxiety and anti-depression behavior, respectively, among rats that were OVX and then received continuous E(2)-replacement, compared to OVX rats administered vehicle or those that experienced a delay in E(2)-replacement. In the mirror maze and light-dark transition task, E(2)-replacement at OVX, or after a delay, reduced anxiety-like behavior. Thus, E(2)-replacement reduced anxiety and depression behavior and improved cognitive performance of aged female rats; however, delay in E(2) treatment influenced whether there were favorable effects of E(2) in some tasks.
随着绝经过渡，卵巢甾体激素雌二醇（E₂）水平下降，这可能会影响老年女性的认知和情感加工，并且有证据表明，使用E₂模拟物的激素替代疗法（HRTs）可能会使部分女性（而非全部）受益。确定对HRTs反应是否为阳性的相关参数备受关注。阳性反应的可能性或许与E₂下降后E₂替代的时机有关。因此，在本研究中，我们利用动物模型对此进行了探究。我们通过检测中年（14个月）或老年（19个月）时接受卵巢切除（OVX）的雌性大鼠的认知（物体放置任务）、焦虑（旷场实验、镜像迷宫、明暗转换任务）和抑郁（强迫游泳任务）行为，来研究长期与短期E₂替代的效果。这些大鼠在手术时或延迟5个月后植入含E₂的植入物，或者在14个月大时接受卵巢切除且从未进行E₂替代。大鼠在20个月大时接受测试。所检验的假设是，与延迟E₂替代相比，在卵巢功能停止时进行E₂替代的大鼠焦虑和抑郁行为会减少，认知能力会提高。与接受OVX并持续给予安慰剂载体的大鼠相比，接受OVX然后持续进行E₂替代的大鼠在物体放置任务中的表现有所改善。在旷场实验和强迫游泳任务中，与接受载体的OVX大鼠或经历E₂替代延迟的大鼠相比，接受OVX然后持续进行E₂替代的大鼠抗焦虑和抗抑郁行为分别有所增加。在镜像迷宫和明暗转换任务中，在OVX时或延迟后进行E₂替代可减少类似焦虑的行为。因此，E₂替代可减少老年雌性大鼠的焦虑和抑郁行为，并改善其认知能力；然而，E₂治疗的延迟会影响E₂在某些任务中是否产生有利影响。
