Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/312622
- author
- Picconi, B ; Centonze, D ; Hakansson, K ; Bernardi, G ; Greengard, P ; Fisone, G ; Cenci Nilsson, Angela LU and Calabresi, P
- organization
- publishing date
- 2003
- 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
- 2016-04-01 17:01:05
- date last changed
- 2022-04-23 01:59:33
@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}}, doi = {{10.1038/nn1040}}, volume = {{6}}, year = {{2003}}, }