NMDA RECEPTOR FUNCTION IN NEUROCHEMISTRY OF PARKINSONISM

继发于多巴胺(DA)丢失的高谷氨酸能状态 提示存在于帕金森氏病(PD)。通过检查 治疗两种神经化学病变(DA变性)的效果 和高谷氨酸能活性)，结果是 这里描述的实验将有助于相关和必要的 神经化学数据显示N-甲基-D- 天冬氨酸(NMDA)受体拮抗剂具有抗帕金森病的作用。 拟议中的研究将检验这种谷氨酸受体的作用。 TiN亚型：完整纹状体和DA去神经支配的纹状体的神经化学。 体内微渗析与高效液相色谱 用电化学检测将被用来监测纹状体 自由活动大鼠的细胞外多巴胺和乙酰胆碱。 单侧6-羟基多巴胺损毁将作为一种 警察。多巴胺的前体左旋多巴(L-多巴)是最有效的 逆转帕金森症状的方法，慢性帕金森病后除外 在这一点上，有害的行为副作用就会出现。 慢性L多巴的这种影响被认为是由于缺乏 纹状体内的神经化学平衡对 基底神经节对感觉运动信息的处理。 该方案中的实验将测试MD-801的能力，一种非 竞争性N-甲基-D-天冬氨酸受体拮抗剂和L-多巴联用 恢复DA和Ach(兴奋性驱动力的指标)之间的平衡 至纹状体)。由此得出的结论 研究将为帕金森病和帕金森病的神经化学病因提供洞察力 NMDA受体拮抗剂的潜在生存能力 治疗这种疾病的方法。

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.