Estrogen-dependent alterations in D2/D3-induced G protein activation in cocaine-sensitized female rats

被引：51

作者：

Febo, M ^{[1
]}

González-Rodríguez, LA ^{[1
]}

Capó-Ramos, DE ^{[1
]}

González-Segarra, NY ^{[1
]}

Segarra, AC ^{[1
]}

机构：

[1] Univ Puerto Rico, Sch Med, Dept Physiol, Neuroendocrinol Lab, San Juan, PR 00936 USA

来源：

JOURNAL OF NEUROCHEMISTRY | 2003年 / 86卷 / 02期

关键词：

estrogen; cocaine sensitization; D2/D3; receptors; female rat; functional autoradiography; nucleus accumbens;

D O I：

10.1046/j.1471-4159.2003.01858.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Estrogen potentiates behavioral sensitization to cocaine in the female rat by mechanisms that remain undetermined. In this study, functional receptor autoradiography was used to investigate estrogen modulation of D-2 /D-3 receptor-induced G protein activation in components of the reward pathway of female rats treated acutely and repeatedly with cocaine. Rats were ovariectomized and given an empty (OVX group) or estradiol benzoate-filled (OVX-EB group) implant. After a week, animals received a daily saline or cocaine injection (15 mg/kg, i.p.) for 5 days, and again on day 13. Animals were killed, and brains were removed and cryosectioned. D-2 /D-3 -stimulated [(35) S]guanosine 5'-(gamma-thio) triphosphate (GTPgammaS) binding was assessed in the cingulate cortex area 2 (Cg2), striatum (STR), nucleus accumbens (NAc) and ventral tegmental area (VTA). OVX-EB rats showed more [(35) S]GTPgammaS binding in the Cg2 and lower binding in the VTA than OVX rats; in the VTA this effect was reversed by a single cocaine injection. Repeated cocaine administration had opposite effects in OVX and OVX-EB rats. [(35) S]GTPgammaS binding was decreased in the Cg2, NAc and STR of OVX-EB rats, and increased in OVX rats. The present results support the hypothesis that cocaine-induced changes in D-2 /D-3 receptor activation are regulated by estrogen. These data suggest that changes in D-2 /D-3 receptor function represent one mechanism by which estrogen regulates behavioral sensitization to cocaine.

引用

页码：405 / 412

页数：8

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