l-DOPA dosage is critically involved in dyskinesia via loss of synaptic depotentiation
Picconi, B ; Paille, V ; Ghiglieri, V ; Bagetta, V ; Barone, I ; Lindgren, Hanna LU ; Bernardi, G ; Cenci Nilsson, Angela LU
and Calabresi, P
(2008)
In Neurobiology of Disease
29(2).
p.327-335
- Abstract
- The emergence of levodopa (l-DOPA)-induced dyskinesia and motor fluctuations represents a major clinical problem in Parkinson's disease (PD). While it has been suggested that the daily dose of l-DOPA can play a critical role, the mechanisms linking l-DOPA dosage to the occurrence of motor complications have not yet been explored. Using an experimental model of PD we have recently demonstrated that long-term l-DOPA treatment leading to the induction of abnormal involuntary movements (AIMs) alters corticostriatal bidirectional synaptic plasticity. Dyskinetic animals, in fact, lack the ability to reverse previously induced long-term potentiation (LTP). This lack of depotentiation has been associated to a defect in erasing unessential motor... (More)
- The emergence of levodopa (l-DOPA)-induced dyskinesia and motor fluctuations represents a major clinical problem in Parkinson's disease (PD). While it has been suggested that the daily dose of l-DOPA can play a critical role, the mechanisms linking l-DOPA dosage to the occurrence of motor complications have not yet been explored. Using an experimental model of PD we have recently demonstrated that long-term l-DOPA treatment leading to the induction of abnormal involuntary movements (AIMs) alters corticostriatal bidirectional synaptic plasticity. Dyskinetic animals, in fact, lack the ability to reverse previously induced long-term potentiation (LTP). This lack of depotentiation has been associated to a defect in erasing unessential motor information. Here chronic l-DOPA treatment was administered at two different doses to hemiparkinsonian rats, and electrophysiological recordings were subsequently performed from striatal spiny neurons. Both low and high doses of l-DOPA restored normal LTP, which was disrupted following dopamine (DA) denervation. By the end of the chronic treatment, however, while the low l-DOPA dose induced AIMs only in half of the rats, the high dose caused motor complications in all the treated animals. Interestingly, the dose-related expression of motor complications was associated with a lack of synaptic depotentiation. Our study provides further experimental evidence to support a direct correlation between the daily dosage of l-DOPA and the induction of motor complications and establishes a critical pathophysiological link between the lack of synaptic depotentiation and the expression of AIMs. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1143371
- author
- Picconi, B
; Paille, V
; Ghiglieri, V
; Bagetta, V
; Barone, I
; Lindgren, Hanna
LU
; Bernardi, G
; Cenci Nilsson, Angela
LU
and Calabresi, P
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Neurobiology of Disease
- volume
- 29
- issue
- 2
- pages
- 327 - 335
- publisher
- Elsevier
- external identifiers
-
- pmid:17997101
- wos:000252647000016
- scopus:38149033506
- ISSN
- 0969-9961
- DOI
- 10.1016/j.nbd.2007.10.001
- language
- English
- LU publication?
- yes
- id
- 91006694-8026-4f1d-aa62-5057f24bfa9e (old id 1143371)
- date added to LUP
- 2016-04-01 12:36:18
- date last changed
- 2022-03-29 03:08:35
@article{91006694-8026-4f1d-aa62-5057f24bfa9e,
abstract = {{The emergence of levodopa (l-DOPA)-induced dyskinesia and motor fluctuations represents a major clinical problem in Parkinson's disease (PD). While it has been suggested that the daily dose of l-DOPA can play a critical role, the mechanisms linking l-DOPA dosage to the occurrence of motor complications have not yet been explored. Using an experimental model of PD we have recently demonstrated that long-term l-DOPA treatment leading to the induction of abnormal involuntary movements (AIMs) alters corticostriatal bidirectional synaptic plasticity. Dyskinetic animals, in fact, lack the ability to reverse previously induced long-term potentiation (LTP). This lack of depotentiation has been associated to a defect in erasing unessential motor information. Here chronic l-DOPA treatment was administered at two different doses to hemiparkinsonian rats, and electrophysiological recordings were subsequently performed from striatal spiny neurons. Both low and high doses of l-DOPA restored normal LTP, which was disrupted following dopamine (DA) denervation. By the end of the chronic treatment, however, while the low l-DOPA dose induced AIMs only in half of the rats, the high dose caused motor complications in all the treated animals. Interestingly, the dose-related expression of motor complications was associated with a lack of synaptic depotentiation. Our study provides further experimental evidence to support a direct correlation between the daily dosage of l-DOPA and the induction of motor complications and establishes a critical pathophysiological link between the lack of synaptic depotentiation and the expression of AIMs.}},
author = {{Picconi, B and Paille, V and Ghiglieri, V and Bagetta, V and Barone, I and Lindgren, Hanna and Bernardi, G and Cenci Nilsson, Angela and Calabresi, P}},
issn = {{0969-9961}},
language = {{eng}},
number = {{2}},
pages = {{327--335}},
publisher = {{Elsevier}},
series = {{Neurobiology of Disease}},
title = {{l-DOPA dosage is critically involved in dyskinesia via loss of synaptic depotentiation}},
url = {{http://dx.doi.org/10.1016/j.nbd.2007.10.001}},
doi = {{10.1016/j.nbd.2007.10.001}},
volume = {{29}},
year = {{2008}},
}