Psychology Department, University of Michigan, Ann Arbor, MI, 48109, USA.
Psychology Department, University of Michigan, Ann Arbor, MI, 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
Horm Behav. 2021 Apr;130:104949. doi: 10.1016/j.yhbeh.2021.104949. Epub 2021 Feb 19.
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 10 mg/kg cocaine, while inhibition of GPER1, via G15, enhanced preference at a 5 mg/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.
性别的不同会影响对精神兴奋剂的反应，女性的反应比男性更大，这是因为性腺激素雌二醇（E2）的存在。大量研究表明，E2 增强了女性对可卡因的觅药和奖赏作用。然而，E2 在男性觅药中的作用尚不清楚。本研究调查了在背外侧纹状体（DLS）中对 E2 受体的药理学操纵对雌雄同体大鼠可卡因偏好的影响。在雄性大鼠中，通过给予 ICI 182,780 或 G1 激活 G 蛋白偶联 E2 受体 1（GPER1），可减弱对 10mg/kg 可卡因的条件性位置偏好，而通过 G15 抑制 GPER1 可增强对 5mg/kg 可卡因剂量的偏好。同样，通过 G1 激活 GPER1 可防止雄性大鼠对 0.1%蔗糖水（SACC）与普通水的偏好。令人惊讶的是，GPER1 的激活并未改变雌性大鼠对可卡因或 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 的数量。未观察到 ERα、ERβ 和 GPER1 的相对 mRNA 表达存在性别差异。然而，在雄性和雌性大鼠中，GPER1 的 mRNA 相对 ERα 和 ERβ 更多。这里呈现的结果表明，E2 通过 GPER1 作用可能对雄性大鼠的药物偏好具有保护作用。
