Priming for L-DOPA-induced abnormal involuntary movements increases the severity of amphetamine-induced dyskinesia in grafted rats

Exp Neurol. 2009 Sep;219(1):355-8. doi: 10.1016/j.expneurol.2009.04.010. Epub 2009 Apr 22.

Abstract

In some patients, graft-induced dyskinesia develops following intrastriatal transplantation of embryonic neural tissue for the treatment of Parkinson's disease. The mechanisms underlying these involuntary movements need to be clarified before this approach to clinical cell therapy can be developed further. We previously found that rats with 6-OHDA lesions, primed with L-DOPA treatment and that have subsequently undergone intrastriatal graft surgery exhibit involuntary movements when subjected to amphetamine. This model of amphetamine-induced AIMs reflects a pattern of post-graft behaviours that in the absence of robust spontaneous GID in the rat is the closest approximation that we currently have available. We now show that they are associated with the chronic administration of L-DOPA prior to the transplantation surgery. We also demonstrate that neither changes in c-fos nor FosB/DeltaFosB expression in the lateral striatum are associated with the expression of these behaviours. Taken together, these data reveal that the severity of abnormal movements elicited by amphetamine in grafted animals may relate to previous L-DOPA exposure and dyskinesia development, but they develop through mechanisms that are independent of FosB/DeltaFosB upregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / toxicity*
  • Animals
  • Antiparkinson Agents / toxicity
  • Brain Tissue Transplantation / adverse effects*
  • Brain Tissue Transplantation / methods
  • Central Nervous System Stimulants / toxicity
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / physiopathology
  • Disease Models, Animal
  • Drug Synergism
  • Dyskinesia, Drug-Induced / metabolism
  • Dyskinesia, Drug-Induced / physiopathology*
  • Female
  • Levodopa / toxicity*
  • Oxidopamine / toxicity
  • Parkinson Disease / drug therapy
  • Parkinson Disease / surgery
  • Parkinsonian Disorders / drug therapy
  • Parkinsonian Disorders / surgery
  • Proto-Oncogene Proteins c-fos / drug effects
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation / adverse effects
  • Stem Cell Transplantation / methods
  • Sympatholytics / toxicity

Substances

  • Antiparkinson Agents
  • Central Nervous System Stimulants
  • Proto-Oncogene Proteins c-fos
  • Sympatholytics
  • Levodopa
  • Oxidopamine
  • Amphetamine