Modulation by estrogen-receptor directed drugs of 5-hydroxytryptamine-2A receptors in rat brain.
Hormonal specificity of modulation of brain 5-HT(2A) 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-HT(2A) 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-HT(2A) receptor expression only in striatum and cortical amygdala. Tamoxifen increased 5-HT(2A) receptor density only in striatum. Raloxifene, an uterine estrogen receptor (ER) antagonist, increased, like estradiol, 5-HT(2A) receptor density and expression in cingulate and frontal cortices, striatum, and nucleus accumbens. Brain regional specificity of estradiol, DHEA, tamoxifen, and raloxifene on 5-HT(2A) receptors was observed which can be dissociated from peripheral activity.
Cyr
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Oncology and Molecular Endocrinology Research Center and Faculté de Pharmacie, Université Laval, Sainte-Foy, Québec, Canada.
Landry
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Di Paolo
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D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D010052:Ovariectomy; D020849:Raloxifene Hydrochloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D004965:Estrogen Antagonists; D044402:Receptor, Serotonin, 5-HT2A; D011960:Receptors, Estrogen; D011985:Receptors, Serotonin; D013629:Tamoxifen; D003687:Dehydroepiandrosterone; D020849:Raloxifene Hydrochloride; D004958:Estradiol