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Effects of pulsatile L-DOPA treatment in the double lesion rat model of striatonigral degeneration (multiple system atrophy)

Stefanova, N ; Lundblad, Martin LU ; Tison, F ; Poewe, W ; Cenci Nilsson, Angela LU orcid and Wenning, GK (2004) In Neurobiology of Disease 15(3). p.630-639
Abstract
We examined the role of a striatal lesion in the development of L-DOPA-induced abnormal involuntary movements (AlMs) using the double lesion rat model of striatonigral degeneration (SND), the underlying neuropathological substrate of parkinsonism associated with multiple system atrophy (MSA-P), in comparison to a Parkinson's disease (PD) rat model. L-DOPA administration reliably induced AlMs in SND and PD rats in a dose-dependent fashion. AlMs occurred significantly earlier in SND compared to PD rats. There was a mild, but significant, transient increase of orolingual AlMs during the first week of low-dose L-DOPA treatment in SND. Whereas L-DOPA significantly improved contralateral forelimb akinesia in PD rats, there was no beneficial... (More)
We examined the role of a striatal lesion in the development of L-DOPA-induced abnormal involuntary movements (AlMs) using the double lesion rat model of striatonigral degeneration (SND), the underlying neuropathological substrate of parkinsonism associated with multiple system atrophy (MSA-P), in comparison to a Parkinson's disease (PD) rat model. L-DOPA administration reliably induced AlMs in SND and PD rats in a dose-dependent fashion. AlMs occurred significantly earlier in SND compared to PD rats. There was a mild, but significant, transient increase of orolingual AlMs during the first week of low-dose L-DOPA treatment in SND. Whereas L-DOPA significantly improved contralateral forelimb akinesia in PD rats, there was no beneficial effect in SND rats. Striatal FosB/DeltaFosB up-regulation in SND and PD rats correlated with the severity of L-DOPA-induced dyskinesias. Pulsatile L-DOPA administration in the double lesion SND rat model replicates salient features of the human disease MSA-P, including loss of the anti-akinetic L-DOPA response and induction of dyskinesias with transient orolingual predominance. (C) 2004 Elsevier Inc. All rights reserved. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
rat model, MSA, dyskinesia, motor improvement, levodopa, FosB
in
Neurobiology of Disease
volume
15
issue
3
pages
630 - 639
publisher
Academic Press
external identifiers
  • pmid:15056471
  • wos:000220796700022
  • scopus:1842419375
  • pmid:15056471
ISSN
0969-9961
DOI
10.1016/j.nbd.2003.11.025
language
English
LU publication?
yes
id
4e564597-3c4f-40ca-9f84-109691121cc7 (old id 281119)
date added to LUP
2016-04-01 11:54:08
date last changed
2025-10-14 10:06:21
@article{4e564597-3c4f-40ca-9f84-109691121cc7,
  abstract     = {{We examined the role of a striatal lesion in the development of L-DOPA-induced abnormal involuntary movements (AlMs) using the double lesion rat model of striatonigral degeneration (SND), the underlying neuropathological substrate of parkinsonism associated with multiple system atrophy (MSA-P), in comparison to a Parkinson's disease (PD) rat model. L-DOPA administration reliably induced AlMs in SND and PD rats in a dose-dependent fashion. AlMs occurred significantly earlier in SND compared to PD rats. There was a mild, but significant, transient increase of orolingual AlMs during the first week of low-dose L-DOPA treatment in SND. Whereas L-DOPA significantly improved contralateral forelimb akinesia in PD rats, there was no beneficial effect in SND rats. Striatal FosB/DeltaFosB up-regulation in SND and PD rats correlated with the severity of L-DOPA-induced dyskinesias. Pulsatile L-DOPA administration in the double lesion SND rat model replicates salient features of the human disease MSA-P, including loss of the anti-akinetic L-DOPA response and induction of dyskinesias with transient orolingual predominance. (C) 2004 Elsevier Inc. All rights reserved.}},
  author       = {{Stefanova, N and Lundblad, Martin and Tison, F and Poewe, W and Cenci Nilsson, Angela and Wenning, GK}},
  issn         = {{0969-9961}},
  keywords     = {{rat model; MSA; dyskinesia; motor improvement; levodopa; FosB}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{630--639}},
  publisher    = {{Academic Press}},
  series       = {{Neurobiology of Disease}},
  title        = {{Effects of pulsatile L-DOPA treatment in the double lesion rat model of striatonigral degeneration (multiple system atrophy)}},
  url          = {{http://dx.doi.org/10.1016/j.nbd.2003.11.025}},
  doi          = {{10.1016/j.nbd.2003.11.025}},
  volume       = {{15}},
  year         = {{2004}},
}