Restoring Dopamine Homeostasis by Acupuncture: A Neurocircuit Model

描述(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，特别是针对帕金森氏病(PD)和药物滥用。针灸被认为是通过恢复身体内环境平衡来缓解疾病的。对于DA障碍，我们假设，如果有过量的DA释放(如在可卡因条件下的大脑)，针灸会减弱DA的释放，如果释放不足(如在PD)，则促进DA的释放。我们提出了一种基于神经元电路模型的解释。在我们的模型中，针刺作为一种外周刺激形式，激活了体感皮质，随后导致纹状体中谷氨酸(Glu)的释放。纹状体Glu随后通过直接支配多巴胺能终末(“推”或增加DA释放)和间接地通过GABA能神经元(“拉”或减少DA释放)来调节DA的释放。针灸将压力在“推”和“拉”力之间转换，以调节DA的释放回到正常的体内平衡水平。我们将首先研究针刺对药物诱导的NAOVE对照动物DA过量和不足状态的影响。幼稚动物的药理学模型为检验我们假设的基本要素提供了一个简化和可控的DA环境。在正常对照组中取得成功后，我们将在帕金森病和药物成瘾的动物模型上测试这一DA动态平衡假说的治疗效果-一项旨在了解针灸在临床治疗中的机制的“高风险和高收益”的科学研究。 公共卫生相关性：这项应用的最终目标是研究针灸治疗多巴胺(DA)相关疾病的机制，特别是针对帕金森氏病(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.