Dopamine agonist-induced dyskinesias are correlated to both firing pattern and frequency alterations of pallidal neurones in the MPTP-treated monkey

Brain. 2001 Mar;124(Pt 3):546-57. doi: 10.1093/brain/124.3.546.


Despite the importance and frequency of levodopa-induced dyskinesias, little is known about their causal mechanisms. In this study, electrophysiological single-unit recordings of the neuronal activity of the globus pallidus internalis (GPi), the main basal ganglia output structure, and the globus pallidus externalis (GPe) were recorded continuously in both normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treated subhuman primates before and after the administration of three dopamine agonists--apomorphine (a dopaminergic mixed agonist), SKF-38393 (a D1 partial agonist) and piribedil (a D2/D3 agonist)--at doses known to induce dyskinesias in the parkinsonian monkey. Changes in both the firing frequency and the firing pattern were analysed in relation to behavioural modifications. In both the normal and the parkinsonian monkey, the three agonists induced a decrease in the mean firing frequency of GPi neurones, although dyskinesias were induced only in the parkinsonian animals. In this situation, the improvement of parkinsonian motor abnormalities was correlated with the decrease in GPi firing frequency, whereas firing pattern changes were concomitant with the onset of dyskinesias. Moreover, firing frequency seemed to be decreased excessively during dyskinesias. The results indicate that the electrophysiological mechanism of dyskinesia involves an excessive decrease in GPi firing frequency and a modification of the firing pattern. However, the similarity between the induced decrease in firing frequency in normal and parkinsonian animals underlines the need for dopamine depletion in the induction of dyskinesias.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Apomorphine / pharmacology
  • Dopamine Agonists / pharmacology*
  • Dyskinesia, Drug-Induced / physiopathology*
  • Female
  • Globus Pallidus / drug effects
  • Globus Pallidus / physiopathology*
  • Macaca fascicularis
  • Neural Pathways / drug effects
  • Neural Pathways / physiopathology
  • Neurons / drug effects
  • Neurons / physiology*
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / physiopathology
  • Piribedil / pharmacology
  • Receptors, Dopamine D1 / agonists
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D2 / metabolism


  • Dopamine Agonists
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Piribedil
  • Apomorphine