The impact of graft size on the development of dyskinesia following intrastriatal grafting of embryonic dopamine neurons in the rat

Neurobiol Dis. 2006 May;22(2):334-45. doi: 10.1016/j.nbd.2005.11.011. Epub 2006 Jan 10.

Abstract

Intrastriatal transplants of embryonic ventral mesencephalon can cause dyskinesia in patients with Parkinson's disease (PD). We assessed the impact of transplant size on the development of graft-induced dyskinesia. Rats with unilateral 6-hydroxydopamine lesions were primed to exhibit L-DOPA-induced dyskinesia. They were then intrastriatally grafted with different quantities of embryonic ventral mesencephalic tissue to give small and large grafts. Without drug treatment, discrete dyskinetic-like movements were observed in most rats with large grafts 2-6 weeks after transplantation, but disappeared later. Amphetamine evoked severe abnormal involuntary movements (AIMs) in grafted animals, which were more striking with large grafts. The AIMs coincided with contralateral rotation, but displayed a different temporal profile and pharmacological properties. Thus, selective dopamine uptake blockade elicited rotational behavior, whereas coadministration of both dopamine and serotonin uptake blockers was required to evoke significant orolingual and limb AIMs. In conclusion, robust and reproducible AIMs were evoked in rats with large grafts by blockade of monoamine reuptake. These AIMs may provide a new tool for assessing dyskinetic effects of neural grafting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / adverse effects
  • Animals
  • Brain Tissue Transplantation / adverse effects*
  • Corpus Striatum / cytology
  • Corpus Striatum / physiopathology*
  • Corpus Striatum / surgery
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Dopamine Agents / adverse effects
  • Dopamine Uptake Inhibitors / pharmacology
  • Dyskinesia, Drug-Induced / etiology
  • Dyskinesia, Drug-Induced / physiopathology*
  • Dyskinesia, Drug-Induced / prevention & control*
  • Female
  • Levodopa / adverse effects
  • Movement / drug effects
  • Movement / physiology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / transplantation*
  • Oxidopamine
  • Parkinsonian Disorders / surgery
  • Rats
  • Rats, Sprague-Dawley
  • Rotation
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Substantia Nigra / cytology
  • Substantia Nigra / embryology
  • Substantia Nigra / transplantation
  • Transplantation Tolerance / drug effects
  • Transplantation Tolerance / physiology

Substances

  • Dopamine Agents
  • Dopamine Uptake Inhibitors
  • Serotonin Uptake Inhibitors
  • Levodopa
  • Oxidopamine
  • Amphetamine
  • Dopamine