Walf Alicia A, Ciriza Iratxe, Garcia-Segura Luis Miguel, Frye Cheryl A
Department of Psychology, Research - The University at Albany - Suny, Albany, NY 12222, USA.
Neuropsychopharmacology. 2008 Jan;33(2):431-40. doi: 10.1038/sj.npp.1301416. Epub 2007 Apr 18.
Estradiol (E(2)) modulates affective and socio-sexual behavior of female rodents. E(2)'s functional effects may involve actions through alpha and beta isoforms of estrogen receptor (ERs). The importance of E(2)'s actions at these isoforms for anxiety (open field, elevated plus maze), depression (forced swim test), and sexual behavior (lordosis) was investigated using an antisense oligonucleotide (AS-ODN) strategy. If ERbeta is required for anti-anxiety and antidepressant-like effects, and ERalpha is required for sexual receptivity, of E(2), then intracerebroventricular administration of AS-ODNs against these ERs should attenuate these effects and reduce immunoreactivity of ERs in brain regions that mediate these behaviors, such as the hippocampus and ventral medial hypothalamus (VMH). Ovariectomized rats were primed with 17beta-E(2) (10 microg) 48 h before testing (hour 0). At hours 0, 24, and 47.5, rats were infused with saline vehicle, scrambled control AS-ODNs, or AS-ODNs targeted against ERalpha and/or ERbeta, and were tested at hour 48. Rats infused with ERbeta AS-ODNs, alone, or with ERalpha AS-ODNs had significantly decreased open field central entries, decreased plus maze open arm time and entries, increased time spent immobile, and decreased time spent swimming in the forced swim test, and decreased ERbeta immunoreactivity in the brain than did rats administered ERalpha AS-ODNs, vehicle, or scrambled AS-ODNs. Rats that were administered ERalpha AS-ODNs, alone, or with ERbeta AS-ODNs had significantly decreased lordosis and decreased ERalpha immunoreactivity in the brain compared to rats administered ERbeta AS-ODNs, vehicle, or scrambled AS-ODNs. Thus, ERbeta and ERalpha may be required for E(2)'s modulation of affective and sexual behavior, respectively.
雌二醇（E₂）可调节雌性啮齿动物的情感和社交性行为。E₂的功能作用可能涉及通过雌激素受体（ERs）的α和β亚型发挥作用。使用反义寡核苷酸（AS - ODN）策略研究了E₂在这些亚型上的作用对焦虑（旷场试验、高架十字迷宫试验）、抑郁（强迫游泳试验）和性行为（脊柱前凸）的重要性。如果E₂的抗焦虑和抗抑郁样作用需要ERβ，而性接受能力需要ERα，那么脑室内注射针对这些ERs的AS - ODNs应会减弱这些作用，并降低介导这些行为的脑区（如海马体和腹内侧下丘脑（VMH））中ERs的免疫反应性。在测试前48小时（第0小时），对去卵巢大鼠用17β - E₂（10微克）进行预处理。在第0、24和47.5小时，给大鼠注射生理盐水、乱序对照AS - ODNs或针对ERα和/或ERβ的AS - ODNs，并在第48小时进行测试。单独注射ERβ AS - ODNs或与ERα AS - ODNs一起注射的大鼠，与注射ERα AS - ODNs、生理盐水或乱序AS - ODNs的大鼠相比，在旷场试验中的中央进入次数显著减少，在高架十字迷宫试验中的开放臂停留时间和进入次数减少，在强迫游泳试验中静止不动的时间增加，游泳时间减少，且脑中ERβ免疫反应性降低。单独注射ERα AS - ODNs或与ERβ AS - ODNs一起注射的大鼠，与注射ERβ AS - ODNs、生理盐水或乱序AS - ODNs的大鼠相比，脊柱前凸显著减少，脑中ERα免疫反应性降低。因此，ERβ和ERα可能分别是E₂调节情感和性行为所必需的。
