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Spatiotemporal pattern of striatal ERK1/2 phosphorylation in a rat model of L-DOPA-induced dyskinesia and the role of dopamine D1 receptors

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Author

Summary, in English

Background: We examined the activation pattern of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and its dependence on D1 versus D2 dopamine receptors in hemiparkinsonian rats treated with 3,4-dihydroxyphenyl-L-alanine (L-DOPA). Methods: 6-Hydroxydopamine-lesioned rats were treated acutely or chronically with L-DOPA in combination with antagonists for D1 or D2 receptors. Development of dyskinesia was monitored in animals receiving chronic drug treatment. Phosphorylation of ERK1/2, mitogen- and stress-activated protein kinase-1 (MSK-1), and the levels of FosB/Delta FosB expression were examined immunohistochemically. Results: L-DOPA treatment caused phosphorylation of ERK1/2 in the dopamine-denervated striatum after acute and chronic administration. Similar levels were observed in matrix and striosomes, and in enkephalin-positive and dynorphin-positive neurons. The severity of dyskinesia was positively correlated with phospho-ERK1/2 levels. Phosphorylation of ERK1/2 and MSK-1 was dose-dependently blocked by SCH23390, but not by raclopride. SCH23390 also inhibited the development of dyskinesia and the induction of FosB/Delta FosB. Conclusions: L-DOPA produces pronounced activation of ERK1/2 signaling in the dopamine-denervated striatum through a D1-receptor-dependent mechanism. This effect is associated with the development of dyskinesia. Phosphorylated ERK1/2 is localized to both dynorphinergic and enkephalinergic striatal neurons, suggesting a general role of ERK1/2 as a plasticity molecule during L-DOPA treatment.

Publishing year

2007

Language

English

Pages

800-810

Publication/Series

Biological Psychiatry

Volume

62

Issue

7

Document type

Journal article

Publisher

Elsevier

Topic

  • Neurosciences

Keywords

  • signaling pathways
  • therapy
  • rodent
  • Parkinson's disease
  • gene transcription
  • motor complications

Status

Published

Research group

  • Basal Ganglia Pathophysiology

ISBN/ISSN/Other

  • ISSN: 0006-3223