l-dopa-induced dyskinesias in unilateral 6-hydroxydopamine-lesioned rats are not modified by excitotoxic lesion of the entopeduncular nucleus and substantia nigra pars reticulata

Synapse. 2013 Jul;67(7):407-14. doi: 10.1002/syn.21652. Epub 2013 Apr 2.

Abstract

l-Dopa-induced dyskinesias (LIDs) are a troublesome complication in Parkinson's disease after long-term therapy and a major reason for surgical treatment. LIDs are effectively eliminated by surgery. We aimed to reproduce such effect in the 6-hydroxydopamine (6-OHDA)-lesioned rat model. Single or combined lesions with quinolinic acid were caused in the entopeduncular nucleus (EP) and substantia nigra pars reticulata (SNr) on 6-hydroxydopamine (6-OHDA)-lesioned rats treated for 3 weeks with l-Dopa (6 mg/kg plus 15 mg/kg benserazide, i.p.). l-Dopa administration was continued for a further week following the lesion and abnormal involuntary movements (AIMs) scored at the end of treatment. Neither the individual lesions of the EP and SNr nor the combined lesions had any antidyskinetic effect nor decreased the total number of rotations. These results suggest that excitotoxic lesions of neurons bodies of the output nuclei of the basal ganglia, which destroy cell bodies and spare fibers of passage, do not induce a beneficial reduction of dyskinesias in contrast to thermolytic lesions in humans (which provokes a complete tissue destruction), thus supporting the possibility that other nuclei or systems might be involved in the antidyskinetic effect of pallidotomy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparkinson Agents / toxicity*
  • Dyskinesia, Drug-Induced / etiology
  • Dyskinesia, Drug-Induced / physiopathology*
  • Entopeduncular Nucleus / drug effects*
  • Entopeduncular Nucleus / pathology
  • Entopeduncular Nucleus / physiopathology
  • Levodopa / toxicity*
  • Male
  • Movement / drug effects
  • Neurons / drug effects
  • Oxidopamine / toxicity
  • Quinolinic Acid / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Substantia Nigra / drug effects*
  • Substantia Nigra / pathology
  • Substantia Nigra / physiopathology

Substances

  • Antiparkinson Agents
  • Levodopa
  • Oxidopamine
  • Quinolinic Acid