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Chapter 22 - Rodent Models of Treatment-Related Complications in Parkinson Disease

Francardo, Veronica LU ; Iderberg, Hanna LU ; Lindgren, Hanna LU and Cenci Nilsson, Angela LU (2014) In Movement Disorders p.373-386
Abstract

Dopamine replacement therapy effectively relieves the typical motor features of Parkinson disease (PD), but it can cause complications that limit its utility. Dyskinesia (abnormal involuntary movements) and motor fluctuations (abrupt changes in the patients' motor status) occur in most PD patients after a few years of 3,4-dihydroxyphenyl-. l-alanine (l-DOPA) pharmacotherapy. Animal models reproducing these motor complications can be obtained in mice and rats if the nigrostriatal dopamine pathway is severely damaged. Within the large arsenal of neurotoxic and genetic models of PD, rodents with unilateral 6-hydroxydopamine lesions have the best characteristics for the sake of modeling l-DOPA-induced dyskinesia. When treated chronically... (More)

Dopamine replacement therapy effectively relieves the typical motor features of Parkinson disease (PD), but it can cause complications that limit its utility. Dyskinesia (abnormal involuntary movements) and motor fluctuations (abrupt changes in the patients' motor status) occur in most PD patients after a few years of 3,4-dihydroxyphenyl-. l-alanine (l-DOPA) pharmacotherapy. Animal models reproducing these motor complications can be obtained in mice and rats if the nigrostriatal dopamine pathway is severely damaged. Within the large arsenal of neurotoxic and genetic models of PD, rodents with unilateral 6-hydroxydopamine lesions have the best characteristics for the sake of modeling l-DOPA-induced dyskinesia. When treated chronically with high doses of l-DOPA, these rodent models may also display motor response alterations reminiscent of the wearing-off fluctuations that occur in PD patients. Because of research performed on these animal models, our understanding of the molecular and biochemical mechanisms of l-DOPA-induced dyskinesia has made great advances, and several pharmacological approaches to treatment have been recently identified and successfully tested in proof-of-concept trials in PD patients. It is now well recognized that dopaminergic therapies for PD also cause nonmotor fluctuations (e.g., abrupt changes in mood and cognitive performance) and impulse control disorders. Valid rodent models of these nonmotor complications need to be developed as an important tool for basic and translational research on the cognitive and psychiatric features of PD.

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author
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
keywords
6-OHDA, Abnormal involuntary movements (AIMs), L-DOPA, L-DOPA-induced dyskinesia, Nonmotor complications, Parkinson disease, Rodent models, Treatment-related complications
in
Movement Disorders
editor
LeDoux, Mark S. and
pages
14 pages
publisher
Elsevier Inc.
external identifiers
  • scopus:84943257103
ISBN
9780124051959
DOI
10.1016/B978-0-12-405195-9.00022-6
language
English
LU publication?
yes
id
b2da68df-8efa-43cf-b8a0-b8be35378921
date added to LUP
2017-04-03 13:35:12
date last changed
2017-11-16 10:46:26
@inbook{b2da68df-8efa-43cf-b8a0-b8be35378921,
  abstract     = {<p>Dopamine replacement therapy effectively relieves the typical motor features of Parkinson disease (PD), but it can cause complications that limit its utility. Dyskinesia (abnormal involuntary movements) and motor fluctuations (abrupt changes in the patients' motor status) occur in most PD patients after a few years of 3,4-dihydroxyphenyl-. l-alanine (l-DOPA) pharmacotherapy. Animal models reproducing these motor complications can be obtained in mice and rats if the nigrostriatal dopamine pathway is severely damaged. Within the large arsenal of neurotoxic and genetic models of PD, rodents with unilateral 6-hydroxydopamine lesions have the best characteristics for the sake of modeling l-DOPA-induced dyskinesia. When treated chronically with high doses of l-DOPA, these rodent models may also display motor response alterations reminiscent of the wearing-off fluctuations that occur in PD patients. Because of research performed on these animal models, our understanding of the molecular and biochemical mechanisms of l-DOPA-induced dyskinesia has made great advances, and several pharmacological approaches to treatment have been recently identified and successfully tested in proof-of-concept trials in PD patients. It is now well recognized that dopaminergic therapies for PD also cause nonmotor fluctuations (e.g., abrupt changes in mood and cognitive performance) and impulse control disorders. Valid rodent models of these nonmotor complications need to be developed as an important tool for basic and translational research on the cognitive and psychiatric features of PD.</p>},
  author       = {Francardo, Veronica and Iderberg, Hanna and Lindgren, Hanna and Cenci Nilsson, Angela},
  editor       = {LeDoux, Mark S.},
  isbn         = {9780124051959},
  keyword      = {6-OHDA,Abnormal involuntary movements (AIMs),L-DOPA,L-DOPA-induced dyskinesia,Nonmotor complications,Parkinson disease,Rodent models,Treatment-related complications},
  language     = {eng},
  month        = {10},
  pages        = {373--386},
  publisher    = {Elsevier Inc.},
  series       = {Movement Disorders},
  title        = {Chapter 22 - Rodent Models of Treatment-Related Complications in Parkinson Disease},
  url          = {http://dx.doi.org/10.1016/B978-0-12-405195-9.00022-6},
  year         = {2014},
}