Increased D 1 dopamine receptor signaling in levodopa‐induced dyskinesia
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 advant...
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| Vydáno v: | Annals of neurology Ročník 57; číslo 1; s. 17 - 26 |
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| Hlavní autoři: | , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
01.01.2005
|
| ISSN: | 0364-5134, 1531-8249 |
| On-line přístup: | Získat plný text |
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| Shrnutí: | 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 |