Estrogenic properties of raloxifene, but not tamoxifen, on D2 and D3 dopamine receptors in the rat forebrain
Estrogenic properties of raloxifene, but not tamoxifen, on D2 and D3 dopamine receptors in the rat forebrain
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DOI：
10.1159/000065951
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发表时间：
2002-10-01
影响因子：
4.1
通讯作者：
Di Paolo, T
中科院分区：
文献类型：
--
作者：
Landry, M;Lévesque, D;Di Paolo, T
本研究通过比较雌二醇与他莫昔芬或雷洛昔芬对多巴胺D-2和D-3受体调节的雌激素特异性。这些化合物具有雌激素和/或抗雌激素活性，这取决于靶组织。雌性大鼠卵巢切除术后两周，我们观察到子宫重量下降60%，这是通过用17 β-雌二醇替代治疗2周来预防的。他莫昔芬或雷洛昔芬治疗2周，子宫重量分别增加35%和15%，但显着低于雌二醇治疗。卵巢切除术减少了前纹状体背外侧部分的多巴胺D2受体特异性结合（20%），而这些受体在纹状体的其他部分以及嗅结节和伏隔核中保持不变。17 β-雌二醇和雷洛昔芬，但不是他莫昔芬治疗阻止这种下降。卵巢切除术后多巴胺D-3受体特异性结合保持不变。然而，雌二醇和雷洛昔芬治疗减少多巴胺D-3受体结合的Calleja岛，核的核心和外壳和前纹状体的背侧部分，与卵巢切除大鼠相比。我们的研究结果表明，雷洛昔芬，而不是他莫昔芬，对多巴胺受体具有激动剂雌激素活性。此外，雌二醇和雷洛昔芬对多巴胺D-2和D-3受体的特异性结合具有相反的作用。版权所有（C）2002 S. Karger AG，巴塞尔。
The present study investigated the estrogenic specificity of the modulation of dopamine D-2 and D-3 receptors by comparing the effects of estradiol with tamoxifen or raloxifene. These compounds have estrogenic and/or antiestrogenic activity depending on the target tissue. Two weeks after ovariectomy of female rats, we observed a 60% decrease in the uterine weight, which was prevented by a replacement therapy of 2 weeks with 17beta-estradiol. A tamoxifen or raloxifene treatment of 2 weeks increased uterine weights by 35 and 15%, respectively, but significantly less than estradiol treatment. Ovariectomy decreased dopamine D2 receptor specific binding (20%) in the dorsolateral part of the anterior striatum and these receptors were left unchanged in the other parts of the striatum as well as in the olfactory tubercle and the nucleus accumbens. 17beta-Estradiol and raloxifene, but not tamoxifen treatment prevented this decrease. Ovariectomy left dopamine D-3 receptor specific binding unchanged. However, estradiol and raloxifene treatment decreased dopamine D-3 receptor binding in the islands of Calleja, the core and shell of the nucleus accumbens and the dorsal part of the anterior striatum, compared with ovariectomized rats. Our results show that raloxifene, but not tamoxifen, has an agonist estrogenic activity on dopamine receptors. Furthermore, estradiol and raloxifene have opposite effects on specific binding to dopamine D-2 and D-3 receptors. Copyright (C) 2002 S. Karger AG, Basel.