Modulation by estrogen-receptor directed drugs of 5-hydroxytryptamine-2A receptors in rat brain
Modulation by estrogen-receptor directed drugs of 5-hydroxytryptamine-2A receptors in rat brain
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DOI：
10.1016/s0893-133x(00)00085-3
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发表时间：
2000-07-01
影响因子：
7.6
通讯作者：
Di Paolo, T
中科院分区：
文献类型：
--
作者：
Cyr, M;Landry, M;Di Paolo, T
通过比较对乳房、骨骼和子宫中雌激素反应具有不同影响的化合物的活性，研究了大脑 5-HT2A 受体调节的激素特异性。两周的雌二醇治疗刺激卵巢切除大鼠的子宫重量降低至完整大鼠值，而与媒介物治疗的卵巢切除大鼠相比，他莫昔芬增加了 29%，雷洛昔芬增加了 16%。在 18 个测试的大脑区域中，卵巢切除术降低了前扣带回、额叶皮质、纹状体和伏隔核中 5-HT2A 受体结合和 mRNA 水平；雌二醇将这种下降恢复到完整的大鼠值。脱氢表雄酮 (DHEA) 仅增加去势大鼠纹状体和皮质杏仁核中 5-HT2A 受体的表达。他莫昔芬仅增加纹状体中的 5-HT2A 受体密度。雷洛昔芬是一种子宫雌激素受体 (ER) 拮抗剂，与雌二醇一样，可增加扣带皮层、额叶皮质、纹状体和伏隔核中 5-HT2A 受体的密度和表达。观察到雌二醇、DHEA、他莫昔芬和雷洛昔芬对 5-HT2A 受体的脑区域特异性，这与外周活动无关。 [神经精神药理学 23:69-78, 2000] (C) 2000 美国神经精神药理学学院。由爱思唯尔科学公司出版。保留所有权利。
Hormonal specificity of modulation of brain 5-HT2A receptors was investigated by comparing activity of compounds with varying effects on estrogen response in breast, bone, and uterus. A two-week estradiol treatment stimulated the decreased uterine weight of ovariectomized rats to intact rat values whereas an increase of 29% with tamoxifen and 16% with raloxifene was observed compared to vehicle-treated ovariectomized rats. In 18 assayed brain regions, ovariectomy decreased 5-HT2A receptor binding and mRNA levels in anterior cingulate and frontal cortices, striatum, and nucleus accumbens; estradiol restored this decrease to intact rat values. Dehydroepiandrosterone (DHEA) increased ovariectomized rats 5-HT2A receptor expression only in striatum and cortical amygdala. Tamoxifen increased 5-HT2A receptor density only in striatum. Raloxifene, an uterine estrogen receptor (ER) antagonist, increased, like estradiol, 5-HT2A receptor density and expression in cingulate and frontal cortices, striatum, and nucleus accumbens. Brain regional specificity of estradiol, DHEA, tamoxifen, and raloxifene on 5-HT2A receptors was observed which can be dissociated from peripheral activity. [Neuropsychopharmacology 23:69-78, 2000] (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. All rights reserved.