甲基苯丙胺对中脑边缘投射多巴胺神经元自发动作电位频率和I_h电流的影响  

Methamphetamine inhibits spontaneous action potential frequency and hyperpolarization-activated cation current in mesolimbic dopaminergic neurons

作　　者：岳庆伟[1] 朱德晓[1] 吴金涛[1] 刘海莉[1] 张静[1] 李贵宝[1] 丁兆习[1] 孙晋浩[1] 

机构地区：[1]山东大学医学院人体解剖学教研室,山东济南250012

出　　处：《山东大学学报（医学版）》2014年第5期10-14,共5页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81371471;81071081);教育部博士点基金(20120131110039);山东省自然科学基金(ZR2010HM051;ZR2012HM026);山东省科技发展计划(2011GSF11810)

摘　　要：目的检测高浓度甲基苯丙胺(MA)对中脑边缘多巴胺神经元自发动作电位频率和超极化激活阳离子电流(Ih)的影响。方法应用立体定位仪将逆行示踪剂注入伏隔核区(NAc),标记投射到该区域的中脑边缘多巴胺神经元,并进行酪氨酸羟化酶(TH)染色鉴定;制备中脑脑片,应用膜片钳技术在全细胞模式下检测MA(10μmol/L)对标记神经元自发动作电位频率及Ih的作用。结果中脑边缘投射多巴胺神经元可被准确示踪标记,呈TH阳性,位于腹侧被盖区(VTA);MA可明显降低其自发动作电位频率(P<0.05),并抑制Ih电流(P<0.05)。结论甲基苯丙胺可抑制中脑边缘多巴胺神经元的自发动作电位频率和Ih电流。Objective To label and identify the mesolimbic dopaminergic neurons and observe the effects of high concentration methamphetamine（MA） on their electrophysiological properties and hyperpolarization-activated cation current（Ih）. Methods Fluorescent retrograde tracer was injected into nucleus accumbens（NAc） with stereotaxic apparatus. The labeled cells were identified with tyrosine hydroxylase（TH） immunohistochemical staining. Whole-cell patchclamp recordings were prepared from the labeled neurons in brain slices with and without M A（10 μmol/L） treatment. Results Mesolimbic neurons projected to NAc were successfully labeled with fluorescence tracer. Immunohistochemical staining showed that labeled cells were TH positive,which mainly distributed in the ventral tegmental area（VTA）. The spontaneous action potential frequency of labeled neurons was obviously reduced by MA treatment（P ＆lt; 0. 05）. Besides,the Ih current was obviously inhibited（P ＆lt; 0. 05） by MA. Conclusion M A inhibits the spontaneous action potential frequency and Ihof mesolimbic dopaminergic neurons.

关 键 词：甲基苯丙胺 多巴胺 神经元 超极化激活阳离子电流 大鼠 

分 类 号：R338.8[医药卫生—人体生理学]