L-dopa-induced dyskinesia: beyond an excessive dopamine tone in the striatum

Sci Rep. 2014 Jan 16;4:3730. doi: 10.1038/srep03730.

Abstract

L-dopa remains the mainstay treatment for Parkinson's disease (PD), although in later stages, treatment is complicated by L-dopa-induced dyskinesias (LID). Current evidence links LID to excessive striatal L-dopa-derived dopamine (DA) release, while the possibility of a direct involvement of L-dopa itself in LID has been largely ignored. Here we show that L-dopa can alter basal ganglia activity and produce LID without enhancing striatal DA release in parkinsonian non-human primates. These data may have therapeutic implications for the management of advanced PD since they suggest that LID could result from diverse mechanisms of action of L-dopa.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / adverse effects
  • Animals
  • Benserazide / adverse effects
  • Benserazide / pharmacokinetics
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopamine Agents / adverse effects*
  • Dopamine Agents / pharmacokinetics
  • Drug Combinations
  • Dyskinesias / etiology*
  • Dyskinesias / metabolism
  • Female
  • Levodopa / adverse effects*
  • Levodopa / pharmacokinetics
  • Macaca mulatta
  • Male
  • Parkinson Disease / metabolism

Substances

  • Dopamine Agents
  • Drug Combinations
  • benserazide, levodopa drug combination
  • Levodopa
  • Benserazide
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Dopamine