Walf Alicia A, Frye Cheryl A
Department of Psychology, The University at Albany-SUNY, Albany, NY 12222, USA.
Pharmacol Biochem Behav. 2007 Feb;86(2):407-14. doi: 10.1016/j.pbb.2006.07.003. Epub 2006 Aug 17.
Estradiol (E(2)) may influence some of the sex differences in neuropsychiatric disorders that emerge post-puberty. Studies in our laboratory, and others, have shown that actions at the beta isoform of estrogen receptor (ER) are important for E(2)'s effects for anxiety and/or depressive behavior. Whether ERbeta in the hippocampus is a target for these effects was investigated in the present study. We hypothesized that if actions at ERbeta in the hippocampus are important for the anti-anxiety and anti-depressive effects, then administration of selective ER modulator (SERMs) with greater affinity for ERbeta than ERalpha to the hippocampus, but not a control region/missed sites (i.e. the ventral tegmental area), should decrease anxiety and depressive behavior, compared to vehicle and that ERalpha-specific SERMs should not have the same effect. To investigate this, ovariectomized (ovx) rats were surgically-implanted with guide cannulae aimed at the hippocampus (target site) or ventral tegmental area (control site). Rats were administered vehicle, or 17beta-E(2) (equal affinity for ERalpha and ERbeta), SERMs with greater affinity for ERalpha vs. ERbeta (17alpha-E(2) or propyl pyrazole triol), or SERMs with greater affinity for ERbeta vs. ERalpha (coumestrol or diarylpropionitrile) to these sites (2 microg/microl/side) before testing in anxiety (open field, elevated plus maze) or depression (forced swim) tasks. ERbeta-selective SERMs to the hippocampus, but not the ventral tegmental area, decreased anxiety and depressive behavior. Rats administered 17beta-E(2) or ERbeta SERMs entered more central squares in an open field, spent more time on the open arms of the plus maze, and spent less time immobile compared to rats administered vehicle. Administration of ERalpha-specific SERMs produced similar effects as vehicle administration. Thus, E(2)'s anti-anxiety and anti-depressive effects may involve ERbeta in the hippocampus.
雌二醇（E₂）可能会影响青春期后出现的神经精神疾病中的一些性别差异。我们实验室及其他机构的研究表明，雌激素受体（ER）β亚型的作用对于E₂在焦虑和/或抑郁行为方面的影响至关重要。本研究调查了海马体中的ERβ是否是这些影响的靶点。我们假设，如果海马体中ERβ的作用对于抗焦虑和抗抑郁作用很重要，那么向海马体而非对照区域/未靶向部位（即腹侧被盖区）给予对ERβ比对ERα具有更高亲和力的选择性ER调节剂（SERM），与给予赋形剂相比，应能减少焦虑和抑郁行为，而ERα特异性SERM不应有相同效果。为了研究这一点，对去卵巢（ovx）大鼠进行手术植入导向套管，分别针对海马体（靶位点）或腹侧被盖区（对照位点）。在进行焦虑（旷场试验、高架十字迷宫试验）或抑郁（强迫游泳试验）任务测试之前，向这些位点给予赋形剂、或对ERα和ERβ具有同等亲和力的17β - E₂、对ERα比对ERβ具有更高亲和力的SERM（17α - E₂或丙基吡唑三醇）、或对ERβ比对ERα具有更高亲和力的SERM（香豆雌酚或二芳基丙腈）（2微克/微升/侧）。向海马体而非腹侧被盖区给予ERβ选择性SERM可减少焦虑和抑郁行为。与给予赋形剂的大鼠相比，给予17β - E₂或ERβ SERM的大鼠在旷场试验中进入更多中央方格，在高架十字迷宫试验的开放臂上停留更多时间，在强迫游泳试验中静止不动的时间更少。给予ERα特异性SERM产生的效果与给予赋形剂相似。因此，E₂的抗焦虑和抗抑郁作用可能涉及海马体中的ERβ。
