Phosphorylation of GluN2B subunits of N-methyl-d-aspartate receptors in the frontal association cortex involved in morphine-induced conditioned place preference in mice

Phosphorylation of GluN2B subunits of N-methyl-d-aspartate receptors in the frontal association cortex involved in morphine-induced conditioned place preference in mice
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额叶联合皮层 N-甲基-d-天冬氨酸受体 GluN2B 亚基的磷酸化参与吗啡诱导的小鼠条件性位置偏好

DOI:
10.1016/j.neulet.2020.135470
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发表时间:
2020-11
影响因子:
2.5
通讯作者:
Tao Li
Tao Li
中科院分区:
医学4区
文献类型:
--
作者:
Gang Chen;Wei Han;Axiang Li;Jing Wang;Jing Xiao;Xin Huang;Khosa Asif Nazir;Qing Shang;Hongyan Qian;Chuchu Qiao;Xinshe Liu;Tao Li

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吗啡是世界上滥用最多的毒品之一,已经造成了严重的社会问题。前额叶皮质(FRA)在记忆形成和药物成瘾中起关键作用。N-甲基-d-天冬氨酸受体(NMDARs)在前额叶皮质(PFC)中含量丰富,许多证据表明含有GluN2B的NMDARs参与了吗啡诱导的条件性位置偏爱(CPP)。然而,GluN2B在吗啡诱导的CPP过程中在FRA中的作用还没有得到充分的研究。在本工作中,我们利用CPP动物模型,检测了磷酸化(p-)GluN2B(丝氨酸;Ser1303)在吗啡诱导的CPP不同时相FRA和NAC中的表达。我们发现p-GluN2B(Ser1303)在FRA的发展和恢复阶段是增加的,但在消亡阶段没有变化。使用GluN2B特异性拮抗剂ifenprodil阻断GluN2B在这两个时相的活性,可减弱吗啡诱导的CPP和恢复。此外,异丙苯地尔还阻断吗啡诱导的FRA中p-GluN2B(Ser1303)的上调。这些结果表明,FRA中含有GluN2B的NMDARs可能参与了对吗啡诱导的CPP的调节和恢复。
Morphine is one of the most abused drugs in the world, which has resulted in serious social problems. The frontal association cortex (FrA) has been shown to play a key role in memory formation and drug addiction.N-Methyl-d-aspartate receptors (NMDARs) are abundant in the prefrontal cortex (PFc) and much evidence indicates that GluN2B-containing NMDARs are involved in morphine-induced conditioned place preference (CPP). However, the function of GluN2B in the FrA during morphine-induced CPP has yet to be fully investigated. In the present work, a CPP animal model was employed to measure the expression of phosphorylated (p-) GluN2B (Serine; Ser 1303) in the FrA and NAc in different phases of morphine-induced CPP. We found that p-GluN2B (Ser 1303) was increased in the FrA during the development and reinstatement phases but unchanged in the extinction phase. The use of ifenprodil, a GluN2B-specific antagonist, to block the activity of GluN2B in the two phases attenuated morphine-induced CPP and reinstatement. Furthermore, ifenprodil also blocked morphine-induced upregulation of p-GluN2B (Ser 1303) in the FrA in both phases. These results indicate that GluN2B-containing NMDARs in the FrA may be involved in the regulation of morphine-induced CPP and reinstatement.
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