甲基苯丙胺依赖对大鼠纹状体RGS4和mGluR5受体信号传导的影响

doi:10.12092/j.issn.1009-2501.2018.05.009

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (5): 536-540.doi: 10.12092/j.issn.1009-2501.2018.05.009

甲基苯丙胺依赖对大鼠纹状体RGS4和mGluR5受体信号传导的影响

赵林波^1,2，隋念含²，李利华³，洪仕君³，邢豫明⁴，赵永娜²

¹云南中医学院信息技术学院，昆明 650500，云南； ²昆明医科大学药学院暨云南省天然药物药理重点实验室，昆明 650500，云南； ³昆明医科大学法医学院，昆明 650500，云南； ⁴云南省公安厅禁毒处毒品技术公安部重点实验室，昆明 650228，云南

收稿日期:2017-11-17 修回日期:2018-01-03 出版日期:2018-05-26 发布日期:2018-05-16
通讯作者: 赵永娜，女，教授，硕士生导师，研究方向：神经药理学。 Tel：15887838797 E-mail：mszhaoyn@163.com
作者简介:赵林波，女，硕士，助教，研究方向：神经药理学。 Tel：13529198070 E-mail：82925224@qq.com
基金资助:
云南省应用基础研究计划联合专项基金资助项目（2012FB023）

Methamphetamine dependent influenced RGS4 and mGluR5 receptor signaling in striatum of rats

ZHAO Linbo ^1,2，SUI Nianhan²，LI Lihua³，HONG Shijun³, XING Yuming ⁴, ZHAO Yongna ²

¹ School of Institute of Information Technology, Yunnan University Of TCM， Kunming 650500，Yunnan, China；² School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Product，Kunming Medical University，Kunming 650500，Yunnan, China； ³School of Forensic Medicine，Kunming Medical University，Kunming 650500，Yunnan, China；⁴ Key Laboratory of Narcotics Technology and Ministry of Police of Yunnan Provincial Police Department，Kunming 650228，Yunnan, China

Received:2017-11-17 Revised:2018-01-03 Online:2018-05-26 Published:2018-05-16

摘要/Abstract

摘要：

目的:研究甲基苯丙胺依赖不同时间对大鼠脑纹状体内G蛋白信号调节因子4(regulator of G-protein signaling 4，RGS4 )和代谢型谷氨酸受体5 (metabotropic receptor 5,mGluR5)信号传导的影响。方法:建立大鼠甲基苯丙胺（methamphetamine,METH）依赖一周组（1W）、两周组(2W)模型，Western blot技术检测大鼠纹状体内RGS4、mGluR5、G蛋白α亚单位蛋白Q(Gαq)、磷脂酶C-β1(phospholipase C-β,PLCβ1)表达水平。结果:METH依赖1W、2W组伴药箱停留时间比生理盐水对照组增加，提示METH依赖模型建成。模型组大鼠纹状体内RGS4蛋白表达水平较生理盐水对照组相比明显下调，而模型组mGluR5蛋白和Gαq蛋白、PLCβ1蛋白表达与生理盐水对照组比较均有不同程度上调，且2W组较1W组改变更明显。结论:METH给药可能导致大鼠脑纹状体内RGS4表达下调，mGluR5表达上调，还可使与mGluR5偶联的Gαq、PLCβ1表达均出现不同程度上调。且METH依赖时间越长，RGS4、mGluR5、 Gαq、PLCβ1的表达水平变化越显著。

关键词: 甲基苯丙胺, 纹状体, 条件位置偏爱, G蛋白信号调节因子4, 代谢型谷氨酸受体5, G蛋白α亚单位蛋白Q, 磷脂酶C-β1

Abstract:

AIM: To investigate whether regulator of G-protein signaling 4(RGS4 ) and metabotropic receptor 5 (mGluR5) expression level changed in striatum of the methamphetamine（METH）-dependent rat and whether the changes were related to the time of METH treatment. METHODS: METH-dependent rat model of one week and two weeks were established. The expression levels of RGS4, mGluR5, Galfaq, PLCbeta1 were detected by Western blot analysis. RESULTS: Rats treated with METH of one week and two weeks spent much more time in the METH-paired chamber than NS control group, suggested that METH-dependent model has successfully established. Compared with NS control group, the expression level of RGS4 in the striatum of rats in model group was down-regulated remarkably. Furthermore, the expression level of mGluR5 and its coupling protein Galfaq, phospholipase C-beta1(PLCbeta1) were up-regulated in different degrees when compared with NS control group, and the change is more remarkable in two weeks group than that of one week group. CONCLUSION: METH treatment down regulate the RGS4 and up regulate mGluR5 in rat striatum, and the expression level of mGluR5 coupling protein Galfaq, PLCbeta. And the longer the time of METH-dependent, the more significant the changes of RGS4, mGluR5, Galfaq, and PLCbeta1.

Key words: methamphetamine, striatum, CPP, RGS4, mGluR5, Galfaq, PLCbeta1

中图分类号:

R971

赵林波，隋念含，李利华，洪仕君，邢豫明，赵永娜. 甲基苯丙胺依赖对大鼠纹状体RGS4和mGluR5受体信号传导的影响[J]. 中国临床药理学与治疗学, 2018, 23(5): 536-540.

ZHAO Linbo，SUI Nianhan，LI Lihua，HONG Shijun, XING Yuming, ZHAO Yongna. Methamphetamine dependent influenced RGS4 and mGluR5 receptor signaling in striatum of rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(5): 536-540.

参考文献

［1］Grant KM , LeVan TD, Wells SM, et al. Methamphetamine-associated psychosis［J］.J Neuroimmune Pharmacol, 2012, 7(1): 113-139.
［2］Schwendt M, McGinty JF, Regulator of G-protein signaling 4 interacts with metabotropic glutamate receptor subtype 5 in rat striatum: relevance to amphetamine behavioral sensitization［J］. J Pharmacol Exp Ther, 2007, 323(2): 650-657.
［3］Traynor J. Regulator of G protein-signaling proteins and addictive drugs［J］. Ann N Y Acad Sci, 2010, 1187: 341-352.
［4］Hooks SB, Martemyanov K, Zachariou V. A role of RGS protein in drug addiction［J］.Biochem Pharmacol, 2008, 75(1): 76-84.
［5］Brown RM,Mustafa S,Mohammed AA,et al.mGluR5 receptor functional interaction and addiction［J］.Front Pharmacol,2012,3:1-9.
［6］洪仕君. 甲基苯丙胺依赖鼠相关脑区多巴胺转运体、D1和D2受体、五羟色胺转运体表达及依赖机制研究［D］.昆明：昆明医学院，2009：19-20.
［7］Tzschentke TM.Measuring reward the conditioned place preference paradigm:a comprehensive review of drug effects, recent progress and new ssues［J］.Prog Neurobiol,1998,56(6):613-672.
［8］Yang PP, Fu YY, Tao PL, et al. Posttreatment of dextromethorphan on methamphetamine-induced drug-seeking and behavioral sensitization in rats ［J］. Synapse, 2012, 66(10):858-869.
［9］许望超．脑奖赏系统研究进展［J］. 广州医药，2008，39(2)：1-2.
［10］鲍云非，郑希耕．纹状体在药物成瘾有关的联想性学习中的作用［J］.生理科学进展，2006，37(2)：165-168.
［11］Gold SJ, Ni YG, Dohlman HG, et al. Regulators of Gprotein signaling (RGS) proteins: regionspecific expression of nine subtypes in rat brain［J］. J Neuro sci 1997, 17(20): 8024-8037.
［12］Bishop GB, Cullinan WE, Curran E, et al. Abused drugs modulate RGS4 mRNA levels in rat brain : comparison between acute drug treatment and a drug challenge after chronic treatment［J］. Neurobiol Dis, 2002, 10(3): 334-343.
［13］Schwendt M, Hearing MC, See RE, et al. Chronic cocaine reduced RGS4 mRNA in rat prefrontal cortex and dorsal striatum［J］. Neuroreport,2007, 18(12): 1261-1265.
［14］Dhami GK, Ferguson SS. Regulation of metabotropic glutamate receptor signaling, desensitization, and endocytosis［J］. Pharmacol Ther, 2006, 111(1): 260-271.
［15］McGeehan AJ, Olive MF. The mGluR5 antagonist MPEP reduces the conditioned rewarding effects of cocaine but not other drugs of abuse［J］. Synapse, 2003, 47(3): 240-242.
［16］Yu MF, Lin TY, Ho WH, et a1. Amphetamine induces differential changes in the gene expression of metabotropic glutamate receptor 5 in cultured cortical and hippocampal neurons［J］. J Mol Neurosci, 2001, 17(1): 13-24.
［17］Schwendt M, Sigmon SA, McGinty JF, et al. RGS4 overexpression in the rat dorsal striatum modulates mGluR5 and amphetamine-mediated behavior and signaling［J］. Psychopharmacol, 2012, 221(4): 621-635.

[1]	蒙国懿，何繁漪，隋念含，赵林波，洪仕君，邢豫明，赵永娜. RGS4和D2受体信号通路相关分子在甲基苯丙胺依赖CPP大鼠纹状体的表达变化[J]. 中国临床药理学与治疗学, 2017, 22(12): 1377-1381.
[2]	高贵珍，吴超，单玲玲，薛宏宇，方雪梅. 硫酸化茯苓多糖对帕金森模型鼠脑组织抗氧化能力的影响[J]. 中国临床药理学与治疗学, 2016, 21(4): 384-388.

甲基苯丙胺依赖对大鼠纹状体RGS4和mGluR5受体信号传导的影响

Methamphetamine dependent influenced RGS4 and mGluR5 receptor signaling in striatum of rats

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 2

编辑推荐

Metrics

本文评价