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.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AT004455-01A2
Application #
7657963
Study Section
Special Emphasis Panel (ZAT1-PK (02))
Program Officer
Khalsa, Partap Singh
Project Start
2009-03-01
Project End
2011-02-28
Budget Start
2009-03-01
Budget End
2010-02-28
Support Year
1
Fiscal Year
2009
Total Cost
$245,625
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Chen, Y Iris; Famous, K; Xu, H et al. (2011) Cocaine self-administration leads to alterations in temporal responses to cocaine challenge in limbic and motor circuitry. Eur J Neurosci 34:800-15
Chen, Y Iris; Choi, Ji-Kyung; Xu, Haibo et al. (2010) Pharmacologic neuroimaging of the ontogeny of dopamine receptor function. Dev Neurosci 32:125-38
Ren, Jiaqian; Xu, Haibo; Choi, Ji-Kyung et al. (2009) Dopaminergic response to graded dopamine concentration elicited by four amphetamine doses. Synapse 63:764-72