Novel actions of estrogen receptor-β on anxiety-related behaviors
Novel actions of estrogen receptor-β on anxiety-related behaviors
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DOI：
10.1210/en.2004-1158
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发表时间：
2005-02-01
期刊：
影响因子：
4.8
通讯作者：
Handa, RJ
中科院分区：
文献类型：
--
作者：
Lund, TD;Rovis, T;Handa, RJ
据报道，雌激素既有引起焦虑的特性，也有缓解焦虑的特性。这种对雌激素的神经生物学反应可能是由两个不同的雌激素受体(ER)系统的存在所介导的，即ERα和ERβ。在大脑中，ERbeta在调节生殖神经内分泌功能中起关键作用，而ERbeta可能在调节非生殖功能中起更重要的作用。为了确定雌激素的抗焦虑作用是否可能通过ERβ介导，我们研究了ER亚型选择性激动剂治疗后的焦虑相关行为。去卵巢雌性大鼠分为4个处理组，每日注射选择性ERβ激动剂二芳基丙腈(DPN)、ERα选择性激动剂丙基吡唑三醇(PPT)、17β-雌二醇或赋形剂，连续4d。注射后，在高架迷宫或开阔场地监测行为。接受DPN治疗的大鼠在两种行为范式中都显示出与焦虑相关的行为显著减少。在高架+迷宫中，DPN显著增加了开放臂进入的次数和在迷宫开放臂上花费的时间。此外，DPN显著减少，而PPT增加，焦虑行为，如排泄物的数量和花在梳理上的时间。在旷野中，与对照组或PPT组相比，接受DPN处理的雌性大鼠有更多的后腿，更多地与新物体互动，在空旷的田野中央花费更多的时间。为了证实DPN的抗焦虑作用是由ER介导的，非选择性ER拮抗剂他莫昔芬单独或与DPN联合使用。他莫昔芬阻断了先前发现的DPN的抗焦虑作用。综上所述，这些发现表明雌激素的抗焦虑特性是由ERbeta介导的。
Estrogens are reported to have both anxiogenic and anxiolytic properties. This dichotomous neurobiological response to estrogens may be mediated by the existence of two distinct estrogen receptor (ER) systems, ERalpha and ERbeta. In brain, ERbeta plays a critical role in regulating reproductive neuroendocrine function, whereas ERbeta may be more important in regulating nonreproductive functions. To determine whether estrogen's anxiolytic actions could be mediated by ERbeta, we examined anxiety-related behaviors after treatment with ER subtype-selective agonists. Ovariectomized female rats, divided into four treatment groups, were injected with the selective ERbeta agonist diarylpropionitrile (DPN), the ERalpha-selective agonist propyl-pyrazole-triol (PPT), 17beta-estradiol, or vehicle daily for 4d. After injections, behavior was monitored in the elevated plus maze or open field. Rats treated with DPN showed significantly decreased anxiety-related behaviors in both behavioral paradigms. In the elevated plus maze, DPN significantly increased the number of open arm entries and time spent on the open arms of the maze. Furthermore, DPN significantly reduced, whereas PPT increased, anxiogenic behaviors such as the number of fecal boli and time spent grooming. In the open field, DPN-treated females made more rears, interacted more with a novel object, and spent more time in the middle of the open field than did control or PPT-treated rats. To confirm that DPN's anxiolytic actions are ER mediated, the nonselective ER antagonist tamoxifen was administered alone or in combination with DPN. Tamoxifen blocked the previously identified anxiolytic actions of DPN. Taken together, these findings suggest that the anxiolytic properties of estrogens are ERbeta mediated.