NMDA RECEPTOR FUNCTION IN NEUROCHEMISTRY OF PARKINSONISM

继发于多巴胺（DA）丢失的高多巴胺能状态已被发现， 提示存在于帕金森病（PD）中。 通过检查 治疗两种神经化学病理（DA变性）的效果 和高血压活动），结果 本文所述的实验将有助于相关和必要的 神经化学数据的一个机构的文献表明，N-甲基-D- 天冬氨酸（NMDA）受体阻断剂具有抗帕金森病作用。 拟议中的研究将检查这种谷氨酸受体的作用， 在完整和去DA神经支配的纹状体的神经化学中， 体内微透析与高效液相色谱 电化学检测将用于监测纹状体 细胞外DA和乙酰胆碱（Ach）在自由移动的大鼠。 单侧6-羟基多巴胺损伤将作为一种动物模型， 警局 左旋多巴（L-DOPA），DA的前体，是最有效的 用于逆转帕金森病症状的方法，除了慢性 给药，此时出现有害的行为副作用。 慢性左旋多巴的这种作用被认为是由于缺乏一种 纹状体中的神经化学平衡， 基底神经节对感觉运动信息的处理。 在这个提议中的实验将测试MD-801的能力，一个非- 竞争性NMDA受体拮抗剂和L-DOPA， 恢复DA和Ach之间的平衡（兴奋性驱动指数 纹状体）中的DA去神经纹状体。 这些结论 研究将提供对PD的神经化学病因学的了解， 也对NMDA受体拮抗剂在 治疗这种疾病。

A hyperglutamatergic state secondary to dopamine (DA) loss has been suggested to exist in Parkinson's disease (PD). By examining the effects of treating both neurochemical pathologies (DA degeneration and hyperglutamatergic activity) of this disease, the results of experiments described herein will contribute relevant and necessary neurochemical data to a body of literature suggesting the N-methyl-D- aspartate (NMDA) receptor blockade has anti-Parkinsonian effects. Proposed studies will examine the role of this glutamate receptor subtype tin the neurochemistry of intact and DA-denervated striatum. In vivo microdialysis and high performance liquid chromatography with electrochemical detection will be used to monitor striatal extracellular DA and acetylcholine (Ach) in freely-moving rats. Unilateral 6-hydroxydopamine lesions will serve as an animal model of PD. Levodopa (L-DOPA), the precursor of DA, is the most effective means for reversing Parkinsonian symptoms, except after chronic administration, at which point deleterious behavioral side effects arise. This effect of chronic L-DOPA is thought to be due to the lack of a neurochemical balance in striatum which is important for the processing of sensorimotor information by the basal ganglia. Experiments in this proposal will test the ability of MD-801, a non- competitive NMDA receptor antagonist, and L-DOPA to collectively restore the balance between DA and Ach (an index of excitatory drive to striatum) in the DA-denervated striatum. Conclusions from these studies will provide insight to the neurochemical etiology of PD and also to the potential viability of NMDA receptor antagonism in the treatment of this disease.