Estrogen Modulates Sexually Dimorphic Contextual Fear Extinction in Rats Through Estrogen Receptor β
Estrogen Modulates Sexually Dimorphic Contextual Fear Extinction in Rats Through Estrogen Receptor β
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DOI：
10.1002/hipo.20581
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发表时间：
2009-01-01
期刊：
影响因子：
3.5
通讯作者：
Hsu, Kuei-Sen
中科院分区：
文献类型：
--
作者：
Chang, Yao-Ju;Yang, Chih-Hao;Hsu, Kuei-Sen
女性和男性在大脑和行为上是不同的。由于遗传和激素因素的结合，这些性别差异在发育早期就出现了，并在整个生命周期中持续存在。以往的研究表明，雄性大鼠的情境恐惧记忆水平显著高于雌性大鼠。然而，它仍然是未知的，是否存在性别差异的背景下的恐惧消退。为了解决这个问题，雄性、正常循环雌性和卵巢切除（OVX）雌性Sprague-Dawley大鼠接受情境恐惧条件反射和消退试验。在这里，我们报告说，虽然雄性大鼠表现出较高水平的冻结比循环雌性大鼠上下文恐惧条件反射后，雌性大鼠在发情前期和发情期阶段的条件反射表现出增强的恐惧消退比雄性大鼠。雌激素受体（ER）β激动剂二芳基丙腈，而不是ER α激动剂丙基吡唑三醇的管理也增强了消除的背景恐惧OVX雌性大鼠，这表明雌激素介导的促进消退涉及ER β的激活。去卵巢雌性大鼠在消退训练前海马内注射雌二醇或二芳基丙腈可显著降低消退试验中的冻结反应水平。此外，雌性大鼠的运动或焦虑状态在卵巢周期中没有变化。这些结果揭示了雌激素在介导性二态性情境恐惧消退中的关键作用，并且雌激素介导的恐惧消退的增强涉及ER β的激活。(C)2009 Wiley-Liss，Inc.
Females and males are different in brain and behavior. These sex differences occur early during development due to a combination of genetic and hormonal factors and continue throughout the life-span. Previous studies revealed that male rats exhibited significantly higher levels of contextual fear memory than female rats. However, it remains unknown whether a sex difference exists in the contextual fear extinction. To address this issue, male, normally cycling female, and ovariectomized (OVX) female Sprague-Dawley rats were subjected to contextual fear conditioning and extinction trials. Here we report that although male rats exhibited higher levels of freezing than cycling female rats after contextual fear conditioning, female rats subjected to conditioning in the proestrus and estrus stage exhibited an enhancement of fear extinction than male rats. An estrogen receptor (ER) beta agonist diarylpropionitrile but not an ER alpha agonist propyl-pyrazole-triol administration also enhanced extinction of contextual fear in OVX female rats, suggesting that estrogen-mediated facilitation of extinction involves the activation of ER beta. Intrahippocampal injection of estradiol or diarylpropionitrile before extinction training in OVX female rats remarkably reduced the levels of freezing response during extinction trials. In addition, the locomotion or anxiety state of female rats does not vary across the ovarian cycle. These results reveal a crucial role for estrogen in mediating sexually dimorphic contextual fear extinction, and that estrogen-mediated enhancement of fear extinction involves the activation of ER beta. (C) 2009 Wiley-Liss, Inc.