左旋多巴诱发异动症大鼠纹状体神经元电生理活动的变化  

Changes of electrophysiological characteristics in striatal neurons of rats with ievodopa-induced dyskinesias

作　　者：管强[1] 曹学兵[2] 孙圣刚[2] 徐岩[2] 王岚[2] 

机构地区：[1]同济大学附属同济医院神经内科,上海200065 [2]华中科技大学同济医学院附属协和医院神经科,武汉430022

出　　处：《中华神经医学杂志》2006年第9期875-879,共5页Chinese Journal of Neuromedicine

基　　金：国家自然科学基金(30300114)

摘　　要：目的探讨纹状体神经元电生理活动的变化在左旋多巴诱发异动症(LID)发生中的作用及意义。方法32只大鼠共分为3组：对照组(n=10),帕金森病(PD)组(n=12),LID组(n=10)。6-羟基多巴胺(6-OHDA)立体定位注射制备偏侧PD大鼠模型,左旋多巴腹腔注射治疗4周诱发LID大鼠模型。两组模型分别尾静脉注射多巴胺D1、D2受体激动剂SKF-38393、quinpirole,受体拮抗剂SCH-23390、haloperidol,采用微电极细胞外记录技术检测纹状体棘状神经元(SMSNs)电生理活动的变化。结果LID组SMSNs的自发性电活动较对照组及PD组明显增多(P＜0．05)。SKF-38393对LID组SMSNs自发性电活动的抑制作用呈浓度依赖性,LID组SMSNs的半抑制浓度(IC50)较PD组明显下降(P＜0．05)。Quinpirole对LID组SMSNs的IC50与PD组相比无显著性差异(P＞0．05)。结论LID大鼠SMSNs的自发性电活动增强,D1受体介导的神经元电活动敏感性增高。Objective To explore the role and significance of electrophysiological characteristics changes of striatal medium-spiny neurons （SMSNs） of rats with levedopa-induced dyskinesias （LID）. Methods Parkinson disease （PD） rats were established by 6-OHDA microinjection stereotaxically. They were treated with chronic intermittent L-dopa celiac injection for 28 days to get the LID rats. Electrophysiological characteristics of SMSNs were studied by extracellular recording in PD, LID and control group. D1 and D2 dopamine agonists（SKF-38393 and quinpirole） and antagonists（SCH-23390 and haloperidol）were injected from tailed vein. The discharge changes caused by D1 and D2 Dopamine Agonists were observed. Results Spontaneous firing rates of SMSNs in striatum of LID group were significantly more than those in control and PD group（P〈0.05）, respectively. In LID group, the inhibitory responses of SMSNs to administration of SKF-38393 were significantly increased and 50% inhibiting concentration （IC50） for SKF-38393 were significantly reduced in LID group as compared to PD group [（0.09±0.02） mg/kg vs （0.05±0.02） mg/kg, P〈0.05]. Between them IC50s for quinpirole had no markedly difference[（0.16±0.08） mg/kg vs （0.14±0.06） mg/kg, P〉0.05]. Condusion The sensitivity of D1 receptor mediated neuronal electric activity was enhanced in LID rats, which may contribute to cause the change of spontaneous electrophysiological characteristics.

关 键 词：左旋多巴 异动症 帕金森病 多巴胺受体 细胞外记录 

分 类 号：R742.5[医药卫生—神经病学与精神病学]