Advanced

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 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)
Please use this url to cite or link to this publication:
author
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
Elsevier
external identifiers
  • pmid:15056471
  • wos:000220796700022
  • scopus:1842419375
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
2007-11-02 09:06:05
date last changed
2017-01-01 04:39:01
@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},
  keyword      = {rat model,MSA,dyskinesia,motor improvement,levodopa,FosB},
  language     = {eng},
  number       = {3},
  pages        = {630--639},
  publisher    = {Elsevier},
  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},
  volume       = {15},
  year         = {2004},
}