Effects of tamoxifen on serotonin transporter and 5-hydroxytryptamine2A receptor binding sites and mRNA levels in the brain of ovariectomized rats with or without acute estradiol replacement

被引:122
作者
Sumner, BEH
Grant, KE
Rosie, R
Hegele-Hartung, C
Fritzemeier, KH
Fink, G
机构
[1] MRC, Brain Metab Unit, Edinburgh EH8 9JZ, Midlothian, Scotland
[2] Res Labs Schering, D-13342 Berlin, Germany
来源
MOLECULAR BRAIN RESEARCH | 1999年 / 73卷 / 1-2期
关键词
serotonin transporter; 5-hydroxytryptamine(2A) receptor; estradiol-17; beta; tamoxifen; estradiol receptor;
D O I
10.1016/S0169-328X(99)00243-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Estradiol-17 beta (E(2)), in its positive feedback mode for gonadotropin release in the female rat, induces expression of the genes for the 5-hydroxytryptamine(2A) receptor (5-HT(2A)R) and the serotonin transporter (SERT) in the dorsal raphe nucleus (DRN) with a concomitant increase in the densities of 5-HT(2A)R and the SERT in rat forebrain. The forebrain regions affected are those which, in humans, are concerned with the control of mood, mental state, cognition and emotion. Here we have used the mixed estradiol agonist/antagonist, tamoxifen, to determine whether this action of estradiol is mediated by cytoplasmic estradiol receptors. Acute treatment (similar to 32 h) of ovariectomized rats with estradiol benzoate (EB) increased significantly the amount of 5-HT(2A)R mRNA and SERT mRNA in the DRN and the densities of 5-HT(2A)R and SERT binding sires in the forebrain. These effects of EB were completely blocked by tamoxifen. Treatment with tamoxifen alone had no effect on either gene expression or the density of binding sites. Together, these data show that tamoxifen acts as a pure estradiol antagonist with respect to serotonergic mechanisms in brain. Detailed analysis of the effects of estradiol and tamoxifen on the DRN showed that SERT gene expression is constitutive only in the posterior DRN; in the anterior DRN, SERT gene expression appears to depend upon estrogen induction which is blocked by tamoxifen. Our findings strongly suggest that estradiol receptors are involved in mediating estradiol action on central serotonergic mechanisms and are relevant for our understanding of the effects of antiestrogens as well as estradiol on mood, mental state and cognition. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:119 / 128
页数:10
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