NMDA receptor subunits change in the prefrontal cortex of pure-opioid and multi-drug abusers: a post-mortem study
NMDA receptor subunits change in the prefrontal cortex of pure-opioid and multi-drug abusers: a post-mortem study
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DOI：
10.1007/s00406-018-0900-8
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发表时间：
2019-04-01
影响因子：
4.7
通讯作者：
Zarrindast, Mohammad-Reza
中科院分区：
文献类型：
--
作者：
Daneshparvar, Hamidreza;Sadat-Shirazi, Mitra-Sadat;Zarrindast, Mohammad-Reza
成瘾是一种慢性复发性疾病，是世界上最重要的问题之一。改变神经递质的水平及其受体的活性，在物质滥用障碍的病理生理学中起着重要作用。众所周知，N-甲基-d-天冬氨酸受体（NMDAR）在成瘾的分子基础中起着重要作用。NMDAR具有两个专性GluN 1和两个区域定位的GluN 2亚基。本研究探讨了药物滥用者前额叶皮层中GluN 1、GluN 2A和GluN 2B蛋白水平的变化。对101例吸毒者的内侧前额叶皮层（mPFC）、外侧前额叶皮层（lPFC）和眶额皮层（OFC）进行了解剖，并与13例非吸毒者进行了比较。Western blotting技术检测NMDAR亚基水平的变化。使用蛋白质印迹技术获得的数据显示，在GluN 1和GluN 2B的水平显着增加，但不是在GluN 2A亚基在所有三个区域（mPFC，lPFC，和OFC）的男子谁患有成瘾相比，适当的控制。这些发现表明，一个新的作用，GluN 1，GluN 2B亚基，而不是GluN 2A亚基的NMDARs，在成瘾的病理生理学，并建议他们的作用在药物诱导的可塑性的NMDARs。
Addiction is a chronic relapsing disorder and is one of the most important issues in the world. Changing the level of neurotransmitters and the activities of their receptors, play a major role in the pathophysiology of substance abuse disorders. It is well-established that N-methyl-d-aspartate receptors (NMDARs) play a significant role in the molecular basis of addiction. NMDAR has two obligatory GluN1 and two regionally localized GluN2 subunits. This study investigated changes in the protein level of GluN1, GluN2A, and GluN2B in the prefrontal cortex of drug abusers. The medial prefrontal cortex (mPFC), lateral prefrontal cortex (lPFC), and orbitofrontal cortex (OFC) were dissected from the brain of 101 drug addicts brains and were compared with the brains of non-addicts (N = 13). Western blotting technique was used to show the alteration in NMDAR subunits level. Data obtained using Western blotting technique showed a significant increase in the level of GluN1 and GluN2B, but not in GluN2A subunits in all the three regions (mPFC, lPFC, and OFC) of men whom suffered from addiction as compared to the appropriate controls. These findings showed a novel role for GluN1, GluN2B subunits, rather than the GluN2A subunit of NMDARs, in the pathophysiology of addiction and suggested their role in the drug-induced plasticity of NMDARs.