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Increased D 1 dopamine receptor signaling in levodopa‐induced dyskinesia
Abstract Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa therapy for Parkinson's disease. Although changes affecting D 1 and D 2 dopamine receptors have been studied in association with this condition, no causal relationship has yet been established. Taki...
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| Published in: | Annals of neurology 2005-01, Vol.57 (1), p.17-26 |
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| Main Authors: | , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
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| Summary: | Abstract
Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa therapy for Parkinson's disease. Although changes affecting D
1
and D
2
dopamine receptors have been studied in association with this condition, no causal relationship has yet been established. Taking advantage of a monkey brain bank constituted to study levodopa‐induced dyskinesia, we report changes affecting D
1
and D
2
dopamine receptors within the striatum of normal, parkinsonian, nondyskinetic levodopa‐treated parkinsonian, and dyskinetic levodopa‐treated parkinsonian animals. Whereas D
1
receptor expression itself is not related to dyskinesia, D
1
sensitivity per D
1
receptor measured by D
1
agonist‐induced [
35
S]GTPγS binding is linearly related to dyskinesia. Moreover, the striata of dyskinetic animals show higher levels of cyclin‐dependent kinase 5 (Cdk5) and of the dopamine‐ and cAMP‐regulated phosphoprotein of 32kDa (DARPP‐32). Our data suggest that levodopa‐induced dyskinesia results from increased dopamine D
1
receptor–mediated transmission at the level of the direct pathway. Ann Neurol 2004 |
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| ISSN: | 0364-5134 1531-8249 |
| DOI: | 10.1002/ana.20296 |