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We have previously shown in rats that estradiol has brain regionally specific effects on AMPA receptors. The present study investigated hormonal specificity of AMPA receptors by comparing the effect of estradiol with tamoxifen or raloxifene, which have varying effects on estrogen response in breast, bone and uterus. Ovariectomy in rats decreased uterus weight which was restored by estradiol treatment, whereas tamoxifen and raloxifene had only a weak effect. Ovariectomy left unchanged AMPA receptor specific binding in rat brain whereas estradiol, tamoxifen and raloxifene decreased it in cortical and striatal regions of ovariectomized rats. Hence, tamoxifen and raloxifene showed agonist estrogenic activity on AMPA receptors in specific brain regions, which can be dissociated from their antagonist estrogenic activity in the periphery.
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Cyr et al. (2001) studied this question.
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