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Chronic intermittent L-DOPA treatment induces changes in dopamine release

Lundblad, Martin LU ; af Bjerken, Sara ; Cenci Nilsson, Angela LU orcid ; 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
; ; ; ; and
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
  • pmid:19196428
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
2016-04-01 14:21:36
date last changed
2022-01-28 00:13:08
@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}},
  keywords     = {{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}},
  doi          = {{10.1111/j.1471-4159.2008.05848.x}},
  volume       = {{108}},
  year         = {{2009}},
}