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Chronic intermittent L-DOPA treatment induces changes in dopamine release

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Author

  • Martin Lundblad
  • Sara af Bjerken
  • Angela Cenci Nilsson
  • Francois Pomerleau
  • Greg A. Gerhardt
  • Ingrid Stromberg

Summary, in English

3,4-Dihydroxyphenyl-l-alanine (l-DOPA)-induced dyskinesia often develops as a side effect of chronic l-DOPA therapy. This study was undertaken to investigate dopamine (DA) release upon l-DOPA treatment. Chronoamperometric measurements were performed in unilaterally DA-depleted rats, chronically treated with l-DOPA, resulting in dyskinetic and non-dyskinetic animals. Normal and lesioned l-DOPA naive animals were used as controls. Potassium-evoked DA releases were significantly reduced in intact sides of animals undertaken chronic l-DOPA treatment, independent on dyskinetic behavior. Acute l-DOPA further attenuated the amplitude of the DA release in the control sides. In DA-depleted striata, no difference was found in potassium-evoked DA releases, and acute l-DOPA did not affect the amplitude. While immunoreactivity to serotonin uptake transporter was higher in lesioned striata of animals displaying dyskinetic behavior, no correlation could be documented between serotonin transporter-positive nerve fiber density and the amplitude of released DA. In conclusions, the amplitude of potassium-evoked DA release is attenuated in intact striatum after chronic intermittent l-DOPA treatment. No change in amplitude was found in DA-denervated sides of either dyskinetic or non-dyskinetic animals, while release kinetics were changed. This indicates the importance of studying DA release dynamics for the understanding of both beneficial and adverse effects of l-DOPA replacement therapy.

Publishing year

2009

Language

English

Pages

998-1008

Publication/Series

Journal of Neurochemistry

Volume

108

Issue

4

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Neurosciences

Keywords

  • chronoamperometry
  • dopamine
  • serotonin transporter
  • 5-hydroxytryptamine or serotonin
  • dyskinesia
  • 4-dihydroxyphenyl-l-alanine induced
  • 3
  • 4-dihydroxyphenyl-l-alanine

Status

Published

Research group

  • Basal Ganglia Pathophysiology

ISBN/ISSN/Other

  • ISSN: 1471-4159