Dysregulated expression of the alternatively spliced variant mRNAs of the mu opioid receptor gene, OPRM1, in the medial prefrontal cortex of male human heroin abusers and heroin self-administering male rats,Journal of Neuroscience Research

当前位置： X-MOL 学术 › J. Neurosci. Res. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Dysregulated expression of the alternatively spliced variant mRNAs of the mu opioid receptor gene, OPRM1, in the medial prefrontal cortex of male human heroin abusers and heroin self-administering male rats
Journal of Neuroscience Research ( IF 2.9 ) Pub Date : 2020-06-07 , DOI: 10.1002/jnr.24640
Taylor G Brown ₁ , Jin Xu ₁ , Yasmin L Hurd _{2,

3} , Ying-Xian Pan ₁

Affiliation

Heroin, a mu agonist, acts through the mu opioid receptor. The mu opioid receptor gene, OPRM1, undergoes extensive alternative splicing, creating an array of splice variants that are conserved from rodent to humans. Increasing evidence suggests that these OPRM1 splice variants are pharmacologically important in mediating various actions of mu opioids, including analgesia, tolerance, physical dependence, rewarding behavior, as well as addiction. In the present study, we examine expression of the OPRM1 splice variant mRNAs in the medial prefrontal cortex (mPFC), one of the major brain regions involved in decision-making and drug-seeking behaviors, of male human heroin abusers and male rats that developed stable heroin-seeking behavior using an intravenous heroin self-administration (SA) model. The results show similar expression profiles among multiple OPRM1 splice variants in both human control subjects and saline control rats, illustrating conservation of OPRM1 alternative splicing from rodent to humans. Moreover, the expressions of several OPRM1 splice variant mRNAs were dysregulated in the postmortem mPFCs from heroin abusers compared to the control subjects. Similar patterns were observed in the rat heroin SA model. These findings suggest potential roles of the OPRM1 splice variants in heroin addiction that could be mechanistically explored using the rat heroin SA model.

中文翻译：

雄性人类海洛因滥用者和海洛因自我给药雄性大鼠内侧前额皮质中 mu 阿片受体基因 OPRM1 的选择性剪接变体 mRNA 的表达失调

海洛因是一种 mu 激动剂，通过 mu 阿片受体发挥作用。 mu 阿片受体基因OPRM1经历广泛的选择性剪接，产生一系列从啮齿动物到人类都保守的剪接变体。越来越多的证据表明，这些OPRM1剪接变体在介导 mu 阿片类药物的各种作用（包括镇痛、耐受、身体依赖性、奖励行为以及成瘾）方面具有重要的药理学作用。在本研究中，我们检测了男性人类海洛因滥用者和雄性大鼠内侧前额叶皮质 (mPFC) 中OPRM1剪接变体 mRNA 的表达，mPFC 是参与决策和寻求药物行为的主要大脑区域之一。使用静脉注射海洛因自我给药（SA）模型来稳定海洛因寻求行为。结果显示，人类对照受试者和盐水对照大鼠的多个OPRM1剪接变体之间存在相似的表达谱，说明从啮齿动物到人类， OPRM1选择性剪接的保守性。此外，与对照组相比，海洛因滥用者死后 mPFC 中几种OPRM1剪接变体 mRNA 的表达失调。在大鼠海洛因 SA 模型中也观察到类似的模式。这些发现表明OPRM1剪接变体在海洛因成瘾中的潜在作用，可以使用大鼠海洛因 SA 模型进行机械探索。

更新日期：2020-06-07

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11