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Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia

Picconi, B; Centonze, D; Hakansson, K; Bernardi, G; Greengard, P; Fisone, G; Cenci Nilsson, Angela LU and Calabresi, P (2003) In Nature Neuroscience 6(5). p.501-506
Abstract
Long-term treatment with the dopamine precursor levodopa (L-DOPA) induces dyskinesia in Parkinson's disease (PD) patients. We divided hemiparkinsonian rats treated chronically with L-DOPA into two groups: one showed motor improvement without dyskinesia, and the other developed debilitating dyskinesias in response to the treatment. We then compared the plasticity of corticostriatal synapses between the two groups. High-frequency stimulation of cortical afferents induced long-term potentiation (LTP) of corticostriatal synapses in both groups of animals. Control and non-dyskinetic rats showed synaptic depotentiation in response to subsequent low-frequency synaptic stimulation, but dyskinetic rats did not. The depotentiation seen in both... (More)
Long-term treatment with the dopamine precursor levodopa (L-DOPA) induces dyskinesia in Parkinson's disease (PD) patients. We divided hemiparkinsonian rats treated chronically with L-DOPA into two groups: one showed motor improvement without dyskinesia, and the other developed debilitating dyskinesias in response to the treatment. We then compared the plasticity of corticostriatal synapses between the two groups. High-frequency stimulation of cortical afferents induced long-term potentiation (LTP) of corticostriatal synapses in both groups of animals. Control and non-dyskinetic rats showed synaptic depotentiation in response to subsequent low-frequency synaptic stimulation, but dyskinetic rats did not. The depotentiation seen in both L-DOPA-treated non-dyskinetic rats and intact controls was prevented by activation of the D1 subclass of dopamine receptors or inhibition of protein phosphatases. The striata of dyskinetic rats contained abnormally high levels of phospho[Thr34]-DARPP-32, an inhibitor of protein phosphatase 1. These results indicate that abnormal information storage in corticostriatal synapses is linked with the development of L-DOPA-induced dyskinesia. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Neuroscience
volume
6
issue
5
pages
501 - 506
publisher
Nature Publishing Group
external identifiers
  • pmid:12665799
  • wos:000182553200017
  • scopus:0037407907
ISSN
1546-1726
DOI
10.1038/nn1040
language
English
LU publication?
yes
id
5cdcc506-36c4-483c-8075-0e01a4510fe7 (old id 312622)
date added to LUP
2007-09-20 10:19:47
date last changed
2018-02-04 04:05:25
@article{5cdcc506-36c4-483c-8075-0e01a4510fe7,
  abstract     = {Long-term treatment with the dopamine precursor levodopa (L-DOPA) induces dyskinesia in Parkinson's disease (PD) patients. We divided hemiparkinsonian rats treated chronically with L-DOPA into two groups: one showed motor improvement without dyskinesia, and the other developed debilitating dyskinesias in response to the treatment. We then compared the plasticity of corticostriatal synapses between the two groups. High-frequency stimulation of cortical afferents induced long-term potentiation (LTP) of corticostriatal synapses in both groups of animals. Control and non-dyskinetic rats showed synaptic depotentiation in response to subsequent low-frequency synaptic stimulation, but dyskinetic rats did not. The depotentiation seen in both L-DOPA-treated non-dyskinetic rats and intact controls was prevented by activation of the D1 subclass of dopamine receptors or inhibition of protein phosphatases. The striata of dyskinetic rats contained abnormally high levels of phospho[Thr34]-DARPP-32, an inhibitor of protein phosphatase 1. These results indicate that abnormal information storage in corticostriatal synapses is linked with the development of L-DOPA-induced dyskinesia.},
  author       = {Picconi, B and Centonze, D and Hakansson, K and Bernardi, G and Greengard, P and Fisone, G and Cenci Nilsson, Angela and Calabresi, P},
  issn         = {1546-1726},
  language     = {eng},
  number       = {5},
  pages        = {501--506},
  publisher    = {Nature Publishing Group},
  series       = {Nature Neuroscience},
  title        = {Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia},
  url          = {http://dx.doi.org/10.1038/nn1040},
  volume       = {6},
  year         = {2003},
}