两种雌二醇给药方案对啮齿动物模型焦虑和抑郁行为及外周组织营养作用的影响
Effects of two estradiol regimens on anxiety and depressive behaviors and trophic effects in peripheral tissues in a rodent model.
作者信息
Walf Alicia A, Frye Cheryl A
机构信息
Department of Psychology, The Centers for Neuroscience and Life Sciences Research, The University at Albany-State University of New York, Albany, New York 12222, USA.
出版信息
Gend Med. 2009 Apr;6(1):300-11. doi: 10.1016/j.genm.2009.04.004.
BACKGROUND
With aging and menopause, which are associated with decreases in ovarian steroids such as 17beta-estradiol (E(2)), women might experience negative psychological symptoms, including anxiety and depression. Some women use E(2)-based therapies to alleviate these symptoms, but E(2) has been associated with trophic effects that might increase vulnerability to some steroid-sensitive cancers, such as breast cancer, in both premenopausal and postmenopausal women.
OBJECTIVE
This study investigated the relationships between the possible beneficial effects of E(2) on anxiety and depressive behaviors concurrent with trophic effects using an animal model of E(2) decline and replacement.
METHODS
Dose-dependent effects of E(2) on affective, sexual, and motor behavior of young adult rats were studied. Ovariectomized (OVX) rats were administered the chemical carcinogen 7,12-dimethylbenz(a) anthracene (DMBA) 1.25 mg or inactive vehicle (vegetable oil; control) by gavage. E(2) (0.03 or 0.09 mg/kg) or vehicle was administered subcutaneously 44 to 48 hours before assessments of anxiety (light-dark transition), depression (forced swim test), sexual (lordosis), and motor (activity monitor) behaviors. Fourteen weeks after carcinogen exposure, E(2) concentrations in plasma and brain regions (cortex, hippocampus, and hypothalamus) were determined. Incidences and numbers of tumors and uterine weight were analyzed.
RESULTS
Administration of E(2) (0.09 mg/kg) was associated with significant increases in antianxiety-like behavior in the light-dark transition task, antidepressant-like behavior in the forced swim test, and physiologic circulating and central E(2) concentrations compared with E(2) (0.03 mg/kg) and vehicle. Compared with vehicle, E(2) (0.9 > 0.3 mg/kg) was associated with significant increases in lordosis and uterine weight. Administration of DMBA was associated with significant increases in the incidences and numbers of tumors; this effect was augmented by E(2)administration.
CONCLUSIONS
Based on the findings in this rat model, the hypothesis that E(2) may be effective in reducing anxiety and depressive behaviors and enhance sexual behavior in OVX rats, concurrent with trophic effects in the periphery, was supported. Moderate physiologic levels of E(2) might have beneficial effects on affective and sexual behaviors in female rodents, but regimens including E(2) might increase tumorigenic capacity.
背景
随着衰老和绝经，与卵巢甾体激素如17β-雌二醇（E₂）水平降低相关，女性可能会出现负面心理症状，包括焦虑和抑郁。一些女性使用基于E₂的疗法来缓解这些症状，但E₂已被证实具有营养作用，这可能会增加绝经前和绝经后女性对某些甾体激素敏感癌症（如乳腺癌）的易感性。
目的
本研究使用E₂下降和替代的动物模型，调查E₂对焦虑和抑郁行为的可能有益影响与营养作用之间的关系。
方法
研究了E₂对成年幼鼠情感、性行为和运动行为的剂量依赖性影响。对去卵巢（OVX）大鼠通过灌胃给予化学致癌物7,12-二甲基苯并(a)蒽（DMBA）1.25 mg或无活性载体（植物油；对照）。在评估焦虑（明暗转换）、抑郁（强迫游泳试验）、性行为（脊柱前凸）和运动（活动监测）行为前44至48小时，皮下注射E₂（0.03或0.09 mg/kg）或载体。致癌物暴露14周后，测定血浆和脑区（皮质、海马和下丘脑）中的E₂浓度。分析肿瘤的发生率和数量以及子宫重量。
结果
与E₂（0.03 mg/kg）和载体相比，给予E₂（0.09 mg/kg）与明暗转换任务中抗焦虑样行为、强迫游泳试验中抗抑郁样行为以及生理循环和中枢E₂浓度的显著增加有关。与载体相比，E₂（0.9 > 0.3 mg/kg）与脊柱前凸和子宫重量的显著增加有关。给予DMBA与肿瘤发生率和数量的显著增加有关；E₂给药增强了这种作用。
结论
基于该大鼠模型的研究结果，支持了E₂可能有效减轻OVX大鼠的焦虑和抑郁行为并增强性行为，同时在外周具有营养作用的假说。适度的生理水平E₂可能对雌性啮齿动物的情感和性行为有有益影响，但包含E₂的方案可能会增加致瘤能力。
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