Synaptic plasticity may underlie l-DOPA induced dyskinesia

Curr Opin Neurobiol. 2018 Feb:48:71-78. doi: 10.1016/j.conb.2017.10.021. Epub 2017 Nov 7.

Abstract

l-DOPA provides highly effective treatment for Parkinson's disease, but l-DOPA induced dyskinesia (LID) is a very debilitating response that eventually is presented by a majority of patients. A central issue in understanding the basis of LID is whether it is due to a response to chronic l-DOPA over years of therapy, and/or due to synaptic changes that follow the loss of dopaminergic neurotransmission and then triggered by acute l-DOPA administration. We review recent work that suggests that specific synaptic changes in the D1 dopamine receptor-expressing direct pathway striatal projection neurons due to loss of dopamine in Parkinson's disease are responsible for LID. Chronic l-DOPA may nevertheless modulate LID through priming mechanisms.

Publication types

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

MeSH terms

  • Animals
  • Antiparkinson Agents / adverse effects*
  • Corpus Striatum / drug effects
  • Corpus Striatum / pathology
  • Disease Models, Animal
  • Dyskinesia, Drug-Induced / pathology*
  • Humans
  • Levodopa / adverse effects*
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Parkinson Disease / drug therapy

Substances

  • Antiparkinson Agents
  • Levodopa