| 宋锐恒,沈建宇,韩伟凯,李贵宝,侯海光,岳庆伟,孙晋浩.中缝背核在甲基苯丙胺诱导小鼠条件性位置偏爱中的作用[J].济宁医学院学报,2022,45(6):381-385 |
| 中缝背核在甲基苯丙胺诱导小鼠条件性位置偏爱中的作用 |
| Role of the dorsal raphe nucleus in methamphetamine-induced conditioned place preference in mice |
| 投稿时间：2022-09-11 |
| DOI：10.3969/j.issn.1000-9760.2022.06.001 |
| 中文关键词: 中缝背核;甲基苯丙胺;条件性位置偏爱;蛋白分析 |
| 英文关键词: Dorsal raphe nucleus;Methamphetamine;Conditioned place preference;Protein analysis |
| 基金项目:国家自然科学基金项目(81871044) |
| 作者 | 单位 | E-mail | | 宋锐恒 | 山东大学基础医学院人体解剖与神经生物学系, 济南 250012 | | | 沈建宇 | 山东大学基础医学院人体解剖与神经生物学系, 济南 250012 | | | 韩伟凯 | 山东大学基础医学院人体解剖与神经生物学系, 济南 250012 | | | 李贵宝 | 山东大学基础医学院人体解剖与神经生物学系, 济南 250012 | | | 侯海光 | 山东大学基础医学院人体解剖与神经生物学系, 济南 250012 | | | 岳庆伟 | 山东大学基础医学院人体解剖与神经生物学系, 济南 250012 | | | 孙晋浩 | 山东大学基础医学院人体解剖与神经生物学系, 济南 250012 | sunjinhao@sdu.edu.cn |
|
| 摘要点击次数: 933 |
| 全文下载次数: 374 |
| 中文摘要: |
| 目的 研究中缝背核(dorsal raphe nucleus,DRN)在甲基苯丙胺(methamphetamine,METH)成瘾中的作用。方法 将C57BL/6J小鼠随机分为METH模型组和对照组。通过腹腔注射METH(2mg/kg)制备条件性位置偏爱(conditioned place preference,CPP)动物模型,对照组注射等量生理盐水。经即刻早基因c-Fos免疫组织化学染色、含Ca2+指示剂病毒载体脑内注射、化学遗传学和蛋白质谱分析等技术,探究METH激活DRN脑区情况及蛋白表达变化,并分析抑制DRN脑区神经元CPP评分的变化。结果 CPP评分显示,METH模型小鼠在伴药箱产生明显偏好(t=4.438,P<0.05)。METH模型组DRN内c-Fos阳性细胞数较对照组显著增多(t=4.065,P<0.05),而且DRN神经元内Ca2+荧光信号明显增强(t=20.50,P<0.001)。通过叠氮平-N-氧化物(clozapine-N-oxide,CNO)腹腔注射(3mg/kg)诱导hM4Di表达抑制DRN神经元兴奋性,明显降低了METH模型组小鼠CPP分数(t=3.26,P<0.05)。蛋白质谱分析在METH模型组DRN脑区筛出了一批差异蛋白,其中突触囊泡蛋白1(Syt1)和细胞黏附分子1(Cadm1)表达升高(均P<0.05);神经束蛋白(Nfasc)和突触小泡蛋白2(SV2)的C亚型表达降低(均P<0.05)。结论 DRN脑区在METH诱导小鼠CPP行为偏好中起着重要作用,METH特异性诱导DRN内与突触相关的蛋白分子的表达,可能与DRN参与的成瘾机制有关。 |
| 英文摘要: |
| Objective To investigate the role of the dorsal raphe nucleus (DRN) in methamphetamine (METH) addiction.Methods C57BL/6J mice were randomly divided into the METH model group and the control group.The conditioned place preference (CPP) animal model was prepared with METH intraperitoneal injection at the dosage of 2mg/kg.The activation of DRN neurons was investigated after METH treatment.Moreover,the CPP score was further analyzed after inhibition of DRN neurons with chemogenetic technique.The protein expression changes were also examined through liquid chromatography mass spectrometry.Results Compared with the control group,METH induced an obvious increasing CPP score compared with the control (t=4.438,P<0.05).In the METH model group,the number of c-Fos positive cells and the Ca2+ fluorescence signal in the DRN were both significantly higher than those of the control group (c-Fos:P<0.05;Ca2+:P<0.001).After injection of clozapine-N-oxide to induce hM4Di expression and inactivation DRN neurons,the CPP score in METH model mice was obviously decreased compared with the control (t=3.260,P<0.05).Furthermore,METH significantly upregulated Syt1 and Cadm1expressions and downregulated Nfascand Sv2c expressions in DRN (all P<0.05).RConclusion DRN exerted an important role in regulating METH induced CPP.METH altered some synapse associated proteins expressions,which possibly participate in METH addiction. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
|
|
|
