Chronic 3,4-dihydroxyphenylalanine treatment induces dyskinesia in aphakia mice, a novel genetic model of Parkinson's disease

Neurobiol Dis. 2007 Jul;27(1):11-23. doi: 10.1016/j.nbd.2007.03.013. Epub 2007 Apr 10.


L-DOPA-induced dyskinesia (LID) is one of the main limitations of long term L-DOPA use in Parkinson's disease (PD) patients. We show that chronic L-DOPA treatment induces novel dyskinetic behaviors in aphakia mouse with selective nigrostriatal deficit mimicking PD. The stereotypical abnormal involuntary movements were induced by dopamine receptor agonists and attenuated by antidyskinetic agents. The development of LID was accompanied by preprodynorphin and preproenkephalin expression changes in the denervated dorsal striatum. Increased FosB-expression was also noted in the dorsal striatum. In addition, FosB expression was noted in the pedunculopontine nucleus and the zona incerta, structures previously not examined in the setting of LID. The aphakia mouse is a novel genetic model with behavioral and biochemical characteristics consistent with those of PD dyskinesia and provides a more consistent, convenient, and physiologic model than toxic lesion models to study the mechanism of LID and to test therapeutic approaches for LID.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / pathology
  • Animals
  • Antiparkinson Agents / pharmacology*
  • Aphakia / complications
  • Aphakia / genetics*
  • Corpus Striatum / pathology
  • Disease Models, Animal*
  • Dynorphins / genetics
  • Dyskinesia, Drug-Induced / complications
  • Dyskinesia, Drug-Induced / genetics
  • Enkephalins / genetics
  • Levodopa / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Neurologic Mutants*
  • Parkinsonian Disorders / complications
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / genetics
  • Parkinsonian Disorders / pathology
  • Protein Precursors / genetics
  • Proto-Oncogene Proteins c-fos / genetics
  • Substantia Nigra / pathology


  • Antiparkinson Agents
  • Enkephalins
  • Fosb protein, mouse
  • Protein Precursors
  • Proto-Oncogene Proteins c-fos
  • pre-prodynorphin
  • Levodopa
  • Dynorphins
  • preproenkephalin