The present study investigated the estrogenic specificity of the modulation of dopamine D2 and D3 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 17β-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. 17β-Estradiol and raloxifene, but not tamoxifen treatment prevented this decrease. Ovariectomy left dopamine D3 receptor specific binding unchanged. However, estradiol and raloxifene treatment decreased dopamine D3 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 D2 and D3 receptors.
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