基因敲除 G 蛋白偶联雌激素受体 1 促进了小鼠获得吗啡诱导的条件性位置偏爱和厌恶。
Genetic knockout of the G protein-coupled estrogen receptor 1 facilitates the acquisition of morphine-induced conditioned place preference and aversion in mice.
机构信息
Ningxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, China; Department of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan, China.
Ningxia Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, China.
出版信息
Biochem Biophys Res Commun. 2020 May 14;525(4):1061-1067. doi: 10.1016/j.bbrc.2020.03.003. Epub 2020 Mar 14.
Drug addiction is considered the pathological usurpation of normal learning and memory. G protein-coupled estrogen receptor 1 (GPER1) plays an important role in normal learning and memory, but the effect of GPER1 on addiction-related pathological memory has not been reported. Our study used GPER1 knockout (GPER1 KO) and wild-type (WT) mice to compare the sensitivity differences of morphine- and sucrose-induced conditioned place preference (CPP) and naloxone-induced conditioned place aversion (CPA), and differences in dopamine (DA) content in the nucleus accumbens (NAc) were determined by high performance liquid chromatography (HPLC). The results showed that GPER1 KO mice showed higher sensitivity to morphine-induced CPP and naloxone-induced CPA, and corresponding to the behavioral effect, the DA content in the NAc of GPER1 KO mice was significantly higher than that of WT mice. Interestingly, the sensitivity of GPER1 KO mice to sucrose-induced CPP did not differ from that of the WT mice, and there was no significant difference in the DA content in the NAc between the two genotypes of mice. GPER1 knockout promoted the formation of morphine addiction-related positive and aversive memory, and its molecular biological mechanism may be associated with increased DA content in the NAc. Therefore, GPER1 plays an important role in the formation of addiction-related pathological memory and may become a potential molecular target for drug addiction therapy.
药物成瘾被认为是对正常学习和记忆的病理性篡夺。G 蛋白偶联雌激素受体 1（GPER1）在正常学习和记忆中发挥重要作用，但 GPER1 对与成瘾相关的病理性记忆的影响尚未报道。我们的研究使用 GPER1 敲除（GPER1 KO）和野生型（WT）小鼠比较吗啡和蔗糖诱导的条件性位置偏爱（CPP）和纳洛酮诱导的条件性位置厌恶（CPA）的敏感性差异，并通过高效液相色谱法（HPLC）测定伏隔核（NAc）中的多巴胺（DA）含量。结果表明，GPER1 KO 小鼠对吗啡诱导的 CPP 和纳洛酮诱导的 CPA 的敏感性更高，与行为效应相对应，GPER1 KO 小鼠 NAc 中的 DA 含量明显高于 WT 小鼠。有趣的是，GPER1 KO 小鼠对蔗糖诱导的 CPP 的敏感性与 WT 小鼠没有差异，两种基因型小鼠 NAc 中的 DA 含量也没有差异。GPER1 敲除促进了吗啡成瘾相关正性和厌恶记忆的形成，其分子生物学机制可能与 NAc 中 DA 含量增加有关。因此，GPER1 在成瘾相关病理性记忆的形成中发挥重要作用，可能成为治疗药物成瘾的潜在分子靶点。
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