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

Research output: Contribution to journalArticle

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.

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Authors
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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • Transplantation, Parkinson's disease, Graft-induced dyskinesia, Amphetamine
Original languageEnglish
Pages (from-to)334-345
JournalNeurobiology of Disease
Volume22
Issue number2
Publication statusPublished - 2006
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Basal Ganglia (013212026), Neuronal Survival (013212041)