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Related Experiment Videos

Levodopa induces dyskinesias in normal squirrel monkeys.

D M Togasaki1, L Tan, P Protell

  • 1The Parkinson's Institute, Sunnyvale, CA 94089, USA. dtogasaki@parkinsonsinstitute.org

Annals of Neurology
|August 17, 2001
PubMed
Summary

Levodopa treatment caused abnormal movements, known as dyskinesias, in healthy squirrel monkeys. This indicates that prior brain damage is not required for levodopa to induce these motor side effects.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Movement Disorders

Background:

  • Levodopa is a primary treatment for Parkinson's disease.
  • Levodopa-induced dyskinesias (LID) are a common and disabling side effect.
  • The necessity of preexisting nigrostriatal damage for LID development is debated.

Purpose of the Study:

  • To investigate if levodopa can induce dyskinesias in subjects without prior neurological damage.
  • To determine if nigrostriatal integrity is essential for levodopa to cause abnormal movements.

Main Methods:

  • Administration of levodopa (with carbidopa) or vehicle to healthy squirrel monkeys over two weeks.
  • Twice-daily oral gavage dosing regimen.
  • Observation and assessment of motor behaviors, including locomotion and dyskinesias.

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Main Results:

  • All levodopa-treated monkeys developed choreoathetoid dyskinesias.
  • No abnormal movements were observed in the vehicle-treated control group.
  • Locomotion was suppressed in levodopa-treated animals, suggesting dyskinesias were specific motor changes, not generalized activation.

Conclusions:

  • Preexisting nigrostriatal damage is not a prerequisite for the development of levodopa-induced dyskinesias.
  • Levodopa can directly induce dyskinesias even in neurologically normal individuals.
  • These findings challenge existing models of dyskinesia pathogenesis.