Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Hippocampus. 2009 Nov;19(11):1142-50. doi: 10.1002/hipo.20581.
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 lifespan. 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 ERalpha 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 ERbeta. 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 ERbeta.
女性和男性在大脑和行为上存在差异。这些性别差异是由于遗传和激素因素的综合作用在发育早期产生的，并持续贯穿整个生命周期。先前的研究表明，雄性大鼠的情景性恐惧记忆水平明显高于雌性大鼠。然而，目前尚不清楚在情景性恐惧消退中是否存在性别差异。为了解决这个问题，雄性、正常循环的雌性和卵巢切除（OVX）雌性 Sprague-Dawley 大鼠接受了情景性恐惧条件反射和消退试验。在这里，我们报告尽管雄性大鼠在情景性恐惧条件反射后比循环雌性大鼠表现出更高水平的冻结，但在动情前期和动情期接受条件反射的雌性大鼠比雄性大鼠表现出更强的恐惧消退增强。雌激素受体（ER）β激动剂二芳基丙腈而不是 ERα激动剂丙基吡唑三醇给药也增强了 OVX 雌性大鼠的情景性恐惧消退，表明雌激素介导的消退增强涉及 ERβ 的激活。在 OVX 雌性大鼠进行消退训练之前，在海马内注射雌二醇或二芳基丙腈可显著降低消退试验过程中的冻结反应水平。此外，雌性大鼠的运动或焦虑状态在卵巢周期内没有变化。这些结果揭示了雌激素在介导性别二态性情景性恐惧消退中的关键作用，并且雌激素介导的恐惧消退增强涉及 ERβ 的激活。
