Restoring Dopamine Homeostasis by Acupuncture: A Neurocircuit Model

通过针灸恢复多巴胺稳态：神经回路模型

• 批准号: 7777828
• 负责人: Yin-Ching Iris Chen
• 金额: $ 21.52万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7777828
• 关键词: Acupuncture procedure; Alternative Medicine; Amphetamines; Animal Model; Animals; Attenuated; Back; Basal Ganglia; Behavior; Biology; Blood Volume; Brain; Brain Mapping; Cerebrum; Clinical; Cocaine; Control Animal; Corpus striatum structure; Coupling; Disease; Dopamine; Dose; Drug Addiction; Effectiveness; Elements; Environment; Feedback; Foundations; Functional Magnetic Resonance Imaging; Future; Glutamates; Goals; Homeostasis; Informal Social Control; Interneurons; Intervention; Knowledge; Lead; Measures; Microdialysis; Modeling; Monitor; Neurons; Neurotransmitters; Output; Parkinson Disease; Pathway interactions; Peripheral; Rattus; Research; Site; Substance abuse problem; System; Testing; Thalamic structure; Therapeutic; Therapeutic Studies; Time; Treatment Efficacy; base; deviant; electrical potential; gamma-Aminobutyric Acid; hemodynamics; high risk; nerve supply; neuronal circuitry; public health relevance; response; restoration; success

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.

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，特别是针对帕金森病（PD）和药物滥用。据说针灸可以通过恢复体内平衡来缓解疾病。对于DA障碍，我们假设如果DA释放过量（如可卡因条件下的大脑），针灸会减弱DA释放，如果DA释放不足（如PD），针灸会增强DA释放。我们提出了一个基于神经回路模型的解释。在我们的模型中，针灸，一种外周刺激，激活体感皮层，随后导致纹状体释放谷氨酸（Glu）。纹状体谷氨酸随后通过直接支配多巴胺能末端的神经（“PUSH”或增加DA释放）和间接通过gaba能神经元（“PULL”或减少DA释放）调节DA释放。针灸改变“推”和“拉”力之间的张力，将DA释放调节到正常的稳态水平。我们将首先从药理学角度研究针刺对小鼠DA过量和不足状态的影响。幼稚动物的药理学模型为验证我们假设的基本要素提供了一个简化和可控的DA环境。在正常对照成功后，我们将在PD和药物成瘾动物模型上验证DA稳态假说的治疗效果，这是一项“高风险高产”的科学研究，旨在了解针灸在临床治疗中的机制。