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Animal models of l-DOPA-induced dyskinesia : the 6-OHDA-lesioned rat and mouse

Tronci, Elisabetta and Francardo, Veronica LU (2017) In Journal of Neural Transmission p.1-8
Abstract

Appearance of l-DOPA-induced dyskinesia (LID) represents a major limitation in the pharmacological therapy with the dopamine precursor l-DOPA. Indeed, the vast majority of parkinsonian patients develop dyskinesia within 9–10 years of l-DOPA oral administration. This makes the discovery of new therapeutic strategies an important need. In the last decades, several animal models of Parkinson’s disease (PD) have been developed, to both study mechanisms underlying PD pathology and treatment-induced side effects (i.e., LID) and to screen for new potential anti-parkinsonian and anti-dyskinetic treatments. Among all the models developed, the 6-OHDA-lesioned rodents represent the models of choice to mimic PD motor symptoms and LID, thanks to... (More)

Appearance of l-DOPA-induced dyskinesia (LID) represents a major limitation in the pharmacological therapy with the dopamine precursor l-DOPA. Indeed, the vast majority of parkinsonian patients develop dyskinesia within 9–10 years of l-DOPA oral administration. This makes the discovery of new therapeutic strategies an important need. In the last decades, several animal models of Parkinson’s disease (PD) have been developed, to both study mechanisms underlying PD pathology and treatment-induced side effects (i.e., LID) and to screen for new potential anti-parkinsonian and anti-dyskinetic treatments. Among all the models developed, the 6-OHDA-lesioned rodents represent the models of choice to mimic PD motor symptoms and LID, thanks to their reproducibility and translational value. Under l-DOPA treatment, rodents sustaining 6-OHDA lesions develop abnormal involuntary movements with dystonic and hyperkinetic features, resembling what seen in dyskinetic PD patients. These models have been extensively validated by the evidence that dyskinetic behaviors are alleviated by compounds reducing dyskinesia in patients and non-human primate models of PD. This article will focus on the translational value of the 6-OHDA rodent models of LID, highlighting their main features, advantages and disadvantages in preclinical research.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
6-OHDA, Dyskinesia, l-DOPA, Parkinson’s disease, Rodent model
in
Journal of Neural Transmission
pages
8 pages
publisher
Springer
external identifiers
  • scopus:85038087645
ISSN
0300-9564
DOI
10.1007/s00702-017-1825-5
language
English
LU publication?
yes
id
fc852870-f475-497b-93b2-1431d9d50d48
date added to LUP
2018-01-03 13:54:16
date last changed
2018-01-10 11:52:46
@article{fc852870-f475-497b-93b2-1431d9d50d48,
  abstract     = {<p>Appearance of l-DOPA-induced dyskinesia (LID) represents a major limitation in the pharmacological therapy with the dopamine precursor l-DOPA. Indeed, the vast majority of parkinsonian patients develop dyskinesia within 9–10 years of l-DOPA oral administration. This makes the discovery of new therapeutic strategies an important need. In the last decades, several animal models of Parkinson’s disease (PD) have been developed, to both study mechanisms underlying PD pathology and treatment-induced side effects (i.e., LID) and to screen for new potential anti-parkinsonian and anti-dyskinetic treatments. Among all the models developed, the 6-OHDA-lesioned rodents represent the models of choice to mimic PD motor symptoms and LID, thanks to their reproducibility and translational value. Under l-DOPA treatment, rodents sustaining 6-OHDA lesions develop abnormal involuntary movements with dystonic and hyperkinetic features, resembling what seen in dyskinetic PD patients. These models have been extensively validated by the evidence that dyskinetic behaviors are alleviated by compounds reducing dyskinesia in patients and non-human primate models of PD. This article will focus on the translational value of the 6-OHDA rodent models of LID, highlighting their main features, advantages and disadvantages in preclinical research.</p>},
  author       = {Tronci, Elisabetta and Francardo, Veronica},
  issn         = {0300-9564},
  keyword      = {6-OHDA,Dyskinesia,l-DOPA,Parkinson’s disease,Rodent model},
  language     = {eng},
  month        = {12},
  pages        = {1--8},
  publisher    = {Springer},
  series       = {Journal of Neural Transmission},
  title        = {Animal models of l-DOPA-induced dyskinesia : the 6-OHDA-lesioned rat and mouse},
  url          = {http://dx.doi.org/10.1007/s00702-017-1825-5},
  year         = {2017},
}