Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia
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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A small number of studies have demonstrated that individuals with Parkinson's disease can acquire some degree of automaticity after simple motor skill practice.
“While a small number of studies have demonstrated that individuals with PD can acquire some degree of automaticity after simple motor skill practice,3, 47”
From Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease (2013) · cites this paper as [47]
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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
- ORCID
- 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
- Licence
- www.springer.com/tdm (tdm)
- 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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