Dopamine Receptor Dependent Subcellular Trafficking of NMDG Glutamate Receptors in Parkinson’s Disease

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Anthone W. Dunah, Ph.D.

The General Hospital Corporation, d/b/a/ Massachusetts General Hospital, Massachusetts

 


Abstract

 


As Parkinson's disease advances, nearly all patients experiece first "wearing off," then the "on-off" phenomenon, known as motor complications of dopaminergic therapy. The current treatments for these troubling symptoms are only partially effective. There is evidence that using drugs that are antagonistic to the receptors for another neurotransmitter, glutamate, may assist in correcting these disabling side effects. Drs. Anthone Dunah and David Standaert at Harvard/Massachusetts General Hospital, Boston, will use the 6-hydroxydopamine-lesioned rat model of Parkinson's disease to try to learn if long-term dopaminergic therapy modifies the function and/or structure of the N-methyl-D-aspartate (NMDA) class of glutamate receptors in Parkinson's disease brains. Substantiated data from this study should help to design better pharmacologic treatments to prevent or reverse the motoric difficulties seen in advancing Parkinson's disease patients.

 

Progress Report (as of 3/2003)

Glutamate, like dopamine, is a neurotransmitter found in the brain. Glutamate, however, is known to be excitatory, thereby causing an “overheating” of cells that may be a causal factor in the occurrence of dyskinesias in patients being treated for their PD symptoms with levodopa compounds. Dr. Anthone W. Dunah (MGH, Boston) learned that rats given the neurotoxin 6-OHDA had changes in their brains’ NMDA receptors. He then used his funds to study alterations of that distribution of receptors by using dopamine agonists, testing at which dopaminergic receptor sites’ intervention best modified the motoric effects. His goal, as is that of many other groups working today is the attenuation of established complications as well as preventing such problems in treated human patients.

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