Activation of G-protein coupled estradiol receptor 1 in the dorsolateral striatum attenuates preference for cocaine and saccharin in male but not female rats.

Activation of G-protein coupled estradiol receptor 1 in the dorsolateral striatum attenuates preference for cocaine and saccharin in male but not female rats.
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DOI:
10.1016/j.yhbeh.2021.104949
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发表时间:
2021-04
影响因子:
3.5
通讯作者:
Becker JB
Becker JB
中科院分区:
医学3区
文献类型:
--
作者:
Quigley JA;Becker JB

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对精神兴奋剂的反应存在性别差异,由于性腺激素雌二醇(E2)的存在,女性比男性表现出更大的反应。广泛的研究表明,E2增强了女性对毒品的寻求和可卡因的奖励特性。然而,E2在男性寻求毒品中的作用还不清楚。本研究探讨了药理学操纵的E2受体在背外侧纹状体(DLS)的偏好可卡因在性腺完整的雄性和雌性大鼠。在雄性中,通过给予ICI 182、780或G1激活G蛋白偶联E2受体1(GPER 1),减弱了对10 mg/kg可卡因的条件性位置偏爱,而通过G15抑制GPER 1,增强了对5 mg/kg可卡因剂量的偏爱。同样,GPER 1激活,通过G1,防止男性形成偏好0.1%糖精(SACC)与白开水。令人惊讶的是,GPER 1的激活并没有改变女性对可卡因或SACC的偏好。这些研究还使用qPCR检查了背侧纹状体中E2受体mRNA的量。ERα、ERβ和GPER 1的相对mRNA表达无性别差异。然而,在男性和女性中,相对于ERα和ERβ,GPER 1 mRNA均较高。这里提出的结果表明,E2,通过GPER 1的作用,可能是保护对药物的偏好,在雄性大鼠。
There are sex differences in the response to psychomotor stimulants, where females exhibit a greater response than males, due to the presence of the gonadal hormone estradiol (E2). Extensive research has shown that E2 enhances drug-seeking and the rewarding properties of cocaine for females. The role of E2 in male drug-seeking, however, is not well understood. The current study investigated pharmacological manipulation of E2 receptors in the dorsolateral striatum (DLS) on preference for cocaine in gonad-intact male and female rats. In males, activation of G-protein coupled E2 receptor 1 (GPER1), via administration of ICI 182,780 or G1, attenuated conditioned place preference for 10mg/kg cocaine, while inhibition of GPER1, via G15, enhanced preference at a 5mg/kg cocaine dose. Similarly, GPER1 activation, via G1, prevented males from forming a preference for 0.1% saccharin (SACC) versus plain water. Surprisingly, activation of GPER1 did not alter preference for cocaine or SACC in females. These studies also examined the quantity of E2 receptor mRNA in the dorsal striatum, using qPCR. No sex differences in relative mRNA expression of ERα, ERβ, and GPER1 were observed. However, there was greater GPER1 mRNA, relative to ERα and ERβ, in both males and females. The results presented here indicate that E2, acting via GPER1, may be protective against drug preference in male rats.
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