苍白球GABAB受体对氟哌啶醇制备帕金森病模型大鼠姿势行为的影响_医学论文.docVIP

苍白球GABAB受体对氟哌啶醇制备帕金森病模型大鼠姿势行为的影响_医学论文 苍白球GABAB受体对氟哌啶醇制备帕金森病模型大鼠姿势行为的影响_医学论文 【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0.5 μL，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=8.5,0.001）；而单侧苍白球微量注射CGP55845可产生明显的对侧偏转行为（u=22.0,0.001）；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=3.5,0.001）。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。 【关键词】 受体 GABA苍白球 帕金森病 运动活动 大鼠 　　［ABSTRACT］ Objective To investigate the effect of GABAB receptor activation in globus pallidus on haloperidolinson’s disease model was made via intraperitoneal administration of haloperidol (1 mg/kg) in rats. A guide cannula was implanted into the globus pallidus. After three days of recovery, either GABAB receptor agonist baclofen, GABAB receptor antagonist CGP55845A, CGP55845A+baclofen, or normal saline in volume of 0.5 μL was unilaterally microinjected into the globus pallidus through the cannula in awake rats. Observation of postural asymmetry was performed within 60 min after microinjection. Results Unilateral microinjection of baclofen (1 mmol/L) caused ipsilateral dystonic posturing in haloperidolinduced parkinsonism rats, which was significantly different from that of control animal (u=8.5,0.001). Microinjection of CGP55845 (0.1 mmol/L) induced contralateral dystonic posturing (u=22.0,0.001), suggesting a tonic activation of GABAB receptor in haloperidolinduced parkinsonian models. Comicroinjection of baclofen and CGP55845 induced a weak contralateral dystonic posturing compared with baclofen alone (u=3.5,0.001). ConclusionBlockade of GABAB 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. ［KEY WORDS］ Receptors, GABA Globus