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Chronic intermittent L-DOPA treatment induces changes in dopamine release

Lundblad, Martin LU ; af Bjerken, Sara; Cenci Nilsson, Angela LU ; Pomerleau, Francois; Gerhardt, Greg A. and Stromberg, Ingrid (2009) In Journal of Neurochemistry 108(4). p.998-1008
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
chronoamperometry, dopamine, serotonin transporter, 5-hydroxytryptamine or serotonin, dyskinesia, 4-dihydroxyphenyl-l-alanine induced, 3, 4-dihydroxyphenyl-l-alanine
in
Journal of Neurochemistry
volume
108
issue
4
pages
998 - 1008
publisher
Wiley-Blackwell
external identifiers
  • wos:000262517100014
  • scopus:58549109655
ISSN
1471-4159
DOI
10.1111/j.1471-4159.2008.05848.x
language
English
LU publication?
yes
id
0f1e21a6-98fa-4b9e-bb49-61b0b32a36fa (old id 1312523)
date added to LUP
2009-03-18 08:55:56
date last changed
2017-04-09 04:03:01
@article{0f1e21a6-98fa-4b9e-bb49-61b0b32a36fa,
  abstract     = {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.},
  author       = {Lundblad, Martin and af Bjerken, Sara and Cenci Nilsson, Angela and Pomerleau, Francois and Gerhardt, Greg A. and Stromberg, Ingrid},
  issn         = {1471-4159},
  keyword      = {chronoamperometry,dopamine,serotonin transporter,5-hydroxytryptamine or serotonin,dyskinesia,4-dihydroxyphenyl-l-alanine induced,3,4-dihydroxyphenyl-l-alanine},
  language     = {eng},
  number       = {4},
  pages        = {998--1008},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  title        = {Chronic intermittent L-DOPA treatment induces changes in dopamine release},
  url          = {http://dx.doi.org/10.1111/j.1471-4159.2008.05848.x},
  volume       = {108},
  year         = {2009},
}