Estrogenic activity of tamoxifen and raloxifene on rat brain AMPA receptors

We have previously shown in rats that estradiol has brain regionally specif ic effects on AMPA receptors. The present study investigated hormonal speci ficity of AMPA receptors by comparing the effect of estradiol with tamoxife n or raloxifene, which have varying effects on estrogen response in breast, bone and uterus. Ovariectomy in rats decreased uterus weight which was res tored by estradiol treatment, whereas tamoxifen and raloxifene had only a w eak effect. Ovariectomy left unchanged AMPA receptor specific binding in ra t brain whereas estradiol, tamoxifen and raloxifene decreased it in cortica l and striatal regions of ovariectomized rats. Hence. tamoxifen and raloxif ene showed agonist estrogenic activity on AMPA receptors in specific brain regions, which can be dissociated from their antagonist estrogenic activity in the periphery. NeuroReport 12:535-539 (C) 2001 Lippincott Williams & Wi lkins.