Restoring Dopamine Homeostasis by Acupuncture: A Neurocircuit Model

描述（由申请人提供）：本申请的最终目的是研究针灸治疗多巴胺（DA）相关疾病的治疗机制，特别针对帕金森病（PD）和药物滥用。针灸据说是通过恢复人体内环境平衡来缓解部分疾病。对于DA障碍，我们假设，针灸衰减DA释放，如果有过量（如在可卡因条件下的大脑）和增强DA释放，如果有一个不足的释放（如在PD）。我们提出了一个基于神经元电路模型的解释。在我们的模型中，针刺，一种外周刺激的形式，激活躯体感觉皮层，随后导致纹状体中的谷氨酸（Glu）释放。纹状体Glu随后通过多巴胺能末梢的直接神经支配（“PUSH”或增加DA释放）和通过GABA能神经元间接调节DA释放（“PUSH”或减少DA释放）。针灸在“推”和“压”力之间转移张力，以调节DA释放回到正常的稳态水平。我们将首先研究针刺对DA过量和缺乏状态的影响。幼稚动物的药理学模型提供了一个简化的和可控的DA环境，用于测试我们的假设的基本要素。在正常对照组成功后，我们将在PD和药物成瘾的动物模型上验证这一DA稳态假说的治疗效果--这是一项旨在了解针灸临床治疗机制的“高风险和高收益”的科学研究。 公共卫生相关性：本申请的最终目的是研究针灸治疗多巴胺（DA）相关疾病的机制，特别是针对帕金森病（PD）和药物滥用。

DESCRIPTION (provided by applicant): The ultimate goal of this application is to study the therapeutic mechanism of acupuncture in treating dopamine (DA) relevant disorders, specifically targeting Parkinson's disease (PD) and substance abuse. Acupuncture is purported to alleviate disorders partly by restoring body homeostasis. For DA disorders, we hypothesize that acupuncture attenuates DA release if there is an excess amount (such as in the cocaine-conditioned brain) and enhances DA release if there is an insufficient release (such as in the PD). We proposed an explanation based on a neuronal circuitry model. In our model, acupuncture, a form of peripheral stimulation, activates somotosensory cortex and subsequently leads to glutamate (Glu) release in the striatum. The striatal Glu subsequently modulates the DA release via direct innervation of the dopaminergic terminals ("PUSH" or increase DA release) and indirectly via GABAnergic neurons ("PULL" or decrease DA release). Acupuncture shifts the strain between the "PUSH" and "PULL" forces to modulate DA release back to a normal homeostatic level. We will first investigate the effect of acupuncture at DA excess and deficient states induced pharmacologically in naove control animals. The pharmacological model of naive animals provides a simplified and controllable DA environment for testing the basic elements of our hypothesis. Upon the success in normal controls, we will test this DA homeostasis hypothesis on animal models of PD and drug addiction in terms of its treatment efficacy --- a "high-risk and high-yield" scientific research aiming for understanding the mechanism of acupuncture in clinical therapy. PUBLIC HEALTH RELEVANCE: The ultimate goal of this application is to study the mechanism of acupuncture in treating dopamine (DA) relevant disorders, specifically targeting Parkinson's disease (PD) and substance abuse.