Hi All,
I just saw this paper, looks interesting (based on the abstract). I have not read it yet to summarize or comment on it.

Glutamate NMDA Receptor Dysregulation in Parkinson's Disease with Dyskinesias

Imtiaz Ahmed; Subrata K. Bose; Nicola Pavese; Anil Ramlackhansingh; Federico Turkheimer; Gary Hotton; Alexander Hammers; David J. Brooks

Authors and Disclosures

Posted: 04/18/2011; Brain. 2011;134(4):979-986. © 2011 Oxford University Press

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* Abstract and Introduction
* Materials and Methods
* Results
* Discussion

* References

Abstract and Introduction
Abstract

Levodopa-induced dyskinesias are a common complication of long-term therapy in Parkinson's disease. Although both pre- and post-synaptic mechanisms seem to be implicated in their development, the precise physiopathology of these disabling involuntary movements remains to be fully elucidated. Abnormalities in glutamate transmission (over expression and phosphorylation of N-methyl-D-aspartate receptors) have been associated with the development of levodopa-induced dyskinesias in animal models of Parkinsonism. The role of glutamate function in dyskinetic patients with Parkinson's disease, however, is unclear. We used 11C-CNS 5161 [N-methyl-3(thyomethylphenyl)cyanamide] positron emission tomography, a marker of activated N-methyl-D-aspartate receptor ion channels, to compare in vivo glutamate function in parkinsonian patients with and without levodopa-induced dyskinesias. Each patient was assessed with positron emission tomography twice, after taking and withdrawal from levodopa. Striatal and cortical tracer uptake was calculated using a region of interest approach. In the 'OFF' state withdrawn from levodopa, dyskinetic and non-dyskinetic patients had similar levels of tracer uptake in basal ganglia and motor cortex. However, when positron emission tomography was performed in the 'ON' condition, dyskinetic patients had higher 11C-CNS 5161 uptake in caudate, putamen and precentral gyrus compared to the patients without dyskinesias, suggesting that dyskinetic patients may have abnormal glutamatergic transmission in motor areas following levodopa administration. These findings are consistent with the results of animal model studies indicating that increased glutamatergic activity is implicated in the development and maintenance of levodopa-induced dyskinesias. They support the hypothesis that blockade of glutamate transmission may have a place in the management of disabling dyskinesias in Parkinson's disease.
Introduction

Dopamine replacement with oral levodopa remains the most effective treatment available for reversing the motor symptoms of Parkinson's disease. However, long-term use of levodopa in patients with Parkinson's disease is invariably associated with the development of abnormal involuntary movements known as dyskinesias, which may become as disabling as the parkinsonian symptoms themselves. A review of the cumulative literature suggests that levodopa-induced dyskinesias (LID) are experienced by 40% of patients with Parkinson's disease 4–6 years after starting levodopa, and up to 90% of patients by 9–15 years of treatment (Ahlskog and Muenter, 2001).

The pathogenic mechanisms underlying LID in Parkinson's disease are still being elucidated. The progressive loss of dopaminergic.................................