苍白球GABA_B受体对氟哌啶醇制备帕金森病模型大鼠姿势行为的影响  

EFFECT OF ACTIVATION OF GABA_B RECEPTOR IN GLOBUS PALLIDUS ON POSTURE BEHAVIOR IN RATS

作　　者：王宏韬[1] 崔巧玲[1] 陈蕾[1] 

机构地区：[1]青岛大学医学院生理学教研室,山东青岛266071

出　　处：《青岛大学医学院学报》2008年第4期286-288,共3页Acta Academiae Medicinae Qingdao Universitatis

基　　金：国家自然科学基金课题(30470545);山东省卫生厅科研基金资助课题(2005HW021)

摘　　要：目的观察苍白球γ-氨基丁酸B型(GABAB)受体激活对氟哌啶醇诱发的帕金森病大鼠姿势行为的影响。方法单侧苍白球埋置套管,恢复3 d后,腹腔注射氟哌啶醇(1 mg/kg)诱发帕金森病僵硬大鼠模型。于4组模型大鼠苍白球分别微量注射生理盐水、GABAB受体激动剂baclofen(1 mmol/L)、GABAB受体阻断剂CGP55845(0.1 mmol/L)、CGP55845和baclofen的混合物,注射体积为0.5μL,观察其偏转行为的变化。结果单侧苍白球微量注射baclofen,大鼠立刻出现明显的同侧偏转行为,与盐水对照组比较,差异有统计学意义(u=8.5,P<0.001);而单侧苍白球微量注射CGP55845可产生明显的对侧偏转行为(u=22.0,P<0.001);同时注入baclofen和CGP55845混合物,动物呈现微弱的对侧偏转行为,与单纯注射baclofen相比,差异有统计学意义(u=3.5,P<0.001)。结论阻断苍白球GABAB受体可减轻氟哌啶醇所致的神经元兴奋性降低,从而解除基底神经节对丘脑及大脑皮质运动区的抑制效应,导致运动功能增强,提示其可能起抗帕金森病的作用。Objective To investigate the effect of GABAB receptor activation in globus pallidus on haloperidol-induced hehavior changes in a rat model of Parkinson＇s disease. Methods A Parkinson＇s disease model was made via intraperitoneal admin- istration of haloperidol （1 mg/kg） in rats. A guide cannula was implanted into the globus pallidus. After three days of recovery, ei- ther GABAa receptor agonist baclofen, GABAa receptor antagonist CGP55845A, CGP55845A＋ baclofen, or normal saline in vo- lume of 0.5 ttL was unilaterally microinjected into the globus pallidus through the cannula in awake rats. Observation of postural a- symmetry was performed within 60 rain after microinjection. Results Unilateral microinjection of baclofen （1 retool/L） caused ipsilateral dystonlc posturing in haloperidol-induced parkinsonism rats, which was significantly different from that of control animal （u：8. 5 ,P（0. 001）. Microinjection of CGP55845 （0.1 retool/L） induced contralateral dystonic posturing （u=22.0,P（0. 001）, suggesting a tonic activation of GABAa receptor in haloperidol-induced parkinsonian models. Co-microinjection of baclofen and CGP55845 induced a weak contralateral dystonic posturing compared with baclofen alone （u = 3. 5, P （ 0. 001 ）. Conclusion Blockade of GABAa receptor dis-inhibits the activity of globus pallidus neurons in haloperidol-induced parkinsonian models, which, in turn, increases the movement output from thalamus and cortex.

关 键 词：受体 GABAB 苍白球 帕金森病 运动活动 大鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]