Cited by 821Parkinson's Disease Mechanisms and TreatmentsNeurological disorders and treatmentsNeurotransmitter Receptor Influence on Behavior

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

Picconi, Barbara, Centonze, Diego, Håkansson, Kerstin, Bernardi, Giorgio, Greengard, Paul, Fisone, Gilberto, Cenci, M. Angela, Calabresi, Paolo·2003·Nature Neuroscience

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.

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Crossref · 10.1038/nn1040

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Authors
Picconi, B., Centonze, D., Håkansson, K., Bernardi, G., Greengard, P., Fisone, G., Cenci, M. A., & Calabresi, P.
Affiliations
  • University of Rome Tor Vergata (IT)
  • Karolinska Institutet (SE)
  • Rockefeller University (US)
  • Lund University (SE)
Corresponding author
Calabresi, Paolo
Venue
Nature Neuroscience
Published
2003-03-31
Volume
6
Issue
5
Pages
501-506
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W1966443363
Cited by
821
References
39
Citations by year
2026: 13 · 2025: 18 · 2024: 15 · 2023: 23 · 2022: 32 · 2021: 33 · 2020: 29 · 2019: 20 · 2018: 37 · 2017: 38 · 2016: 30 · 2015: 49 · 2014: 52 · 2013: 35 · 2012: 42
FWCI
23.23
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • National Institute of Mental Health (MH40899, P01MH040899)
  • National Institute on Drug Abuse (DA10044, P01DA010044)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
levodopa-induced dyskinesia, Parkinson's disease, corticostriatal synapses, synaptic plasticity, long-term potentiation, depotentiation, dopamine D1 receptor, protein phosphatase 1, DARPP-32, striatum, bidirectional synaptic plasticity, hemiparkinsonian rats
MeSH terms
Animals, Corpus Striatum, Dyskinesia, Drug-Induced, Levodopa, Male, Nerve Tissue Proteins, Synaptic Transmission, Neuronal Plasticity, Phosphoproteins, Phosphorylation, Rats, Wistar, Excitatory Postsynaptic Potentials, Parkinsonian Disorders, Rats, Dopamine and cAMP-Regulated Phosphoprotein 32, In Vitro Techniques

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