The impact of graft size on the development of dyskinesia following intrastriatal grafting of embryonic dopamine neurons in the rat.
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.
Lane
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Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden. emma.lane@med.lu.se
Winkler
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Brundin
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Cenci
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D000661:Amphetamine / Q000009:adverse effects; D000818:Animals; D016380:Brain Tissue Transplantation / Q000009:adverse effects*; D003342:Corpus Striatum / Q000166:cytology / Q000503:physiopathology* / Q000601:surgery; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000009:adverse effects; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D005260:Female; D007980:Levodopa / Q000009:adverse effects; D009068:Movement / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology / Q000196:embryology / Q000637:transplantation; D023001:Transplantation Tolerance / Q000187:drug effects / Q000502:physiology
D000661:Amphetamine; D004298:Dopamine; D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D007980:Levodopa; D016627:Oxidopamine; D017367:Selective Serotonin Reuptake Inhibitors