Walf Alicia A, Frye Cheryl A
Department of Psychology, The University at Albany-SUNY, Albany, NY 12222, USA.
Neuropsychopharmacology. 2006 Jun;31(6):1097-111. doi: 10.1038/sj.npp.1301067.
Estrogen (E2) has many effects in the central nervous system, including effects on anxiety and depression behavior. This review will address effects of E2 on behaviors related to anxiety and depression in women and animal models and include recent findings from our laboratory related to this topic. E2's antianxiety and antidepressant-like effects may depend upon many factors, including the regimen of E2 utilized and interactions with the hypothalamic-pituitary-adrenal axis. Brain targets for E2's effects on anxiety and depression include the hippocampus and amygdala. Administration of E2, compared to vehicle, subcutaneously or to the hippocampus or amygdala of ovariectomized rats decreases anxiety and depressive behavior. Intracellular estrogen receptors (ERs) may be important for E2's anxiolytic and antidepressant-like effects. Administration of an ER antagonist to the hippocampus, but not amygdala, increases anxiety and depression behavior of naturally receptive female rats. Studies utilizing ER knockout mice or selective ER modulators suggest that ER-mediated effects of E2 on anxiety and depressive behavior may require ERbeta. In addition, the behavioral effects of E2 may involve membrane actions and/or changes in cell cycle processes involved in energy expenditure. Elucidating the mechanisms by which E2 affects anxiety and depression is important in order to enhance its therapeutic potential. It is particularly important to investigate the putative receptor mechanisms and brain targets for E2 to determine whether mood-enhancing effects of E2 can occur without deleterious proliferative effects in reproductive tissues.
雌激素（E2）在中枢神经系统中有多种作用，包括对焦虑和抑郁行为的影响。本综述将探讨E2对女性及动物模型中与焦虑和抑郁相关行为的影响，并纳入我们实验室最近在该主题上的研究发现。E2的抗焦虑和抗抑郁样作用可能取决于许多因素，包括所使用的E2给药方案以及与下丘脑 - 垂体 - 肾上腺轴的相互作用。E2对焦虑和抑郁产生影响的脑靶点包括海马体和杏仁核。与给予赋形剂相比，对去卵巢大鼠皮下注射E2，或向其海马体或杏仁核注射E2，均可降低焦虑和抑郁行为。细胞内雌激素受体（ERs）可能对E2的抗焦虑和抗抑郁样作用至关重要。向海马体而非杏仁核注射ER拮抗剂，会增加自然处于发情期的雌性大鼠的焦虑和抑郁行为。利用ER基因敲除小鼠或选择性ER调节剂进行的研究表明，E2通过ER介导对焦虑和抑郁行为产生的影响可能需要ERβ。此外，E2的行为效应可能涉及膜作用和/或与能量消耗相关的细胞周期过程的变化。阐明E2影响焦虑和抑郁的机制对于增强其治疗潜力很重要。研究E2的假定受体机制和脑靶点，以确定E2在不产生生殖组织有害增殖效应的情况下是否能产生改善情绪的作用，尤为重要。
