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

Veronica Francardo, Hanna Iderberg, Hanna Lindgren, Angela Cenci Nilsson

Research output: Chapter in Book/Report/Conference proceedingBook chapterpeer-review

1 Citation (SciVal)

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 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.

Original languageEnglish
Title of host publicationMovement Disorders
Subtitle of host publicationGenetics and Models
EditorsMark S. LeDoux
PublisherElsevier
Pages373-386
Number of pages14
Edition2nd
ISBN (Print)9780124051959
DOIs
Publication statusPublished - 2014 Oct 29

Subject classification (UKÄ)

  • Neurosciences

Keywords

  • 6-OHDA
  • Abnormal involuntary movements (AIMs)
  • L-DOPA
  • L-DOPA-induced dyskinesia
  • Nonmotor complications
  • Parkinson disease
  • Rodent models
  • Treatment-related complications

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