Rodent models of treatment-induced motor complications in Parkinson's disease

Treatment-induced motor complications represent a major clinical problem in Parkinson's disease (PD). Pharmacological dopamine (DA) replacement with L-dopa causes motor fluctuations and abnormal involuntary movements (dyskinesia) in the vast majority of the patients. Intrastriatal grafts of embryonic dopaminergic neurons can cause dyskinesia too, as shown by clinical trials of neural transplantation in PD. Animals models of these complications can be produced in rats and mice in which the nigrostriatal DA pathway has been severely damaged. Rodent models allow investigators to explore mechanistic hypotheses at the cellular and molecular level. Moreover, the rat model of L-dopa-induced abnormal involuntary movements shows both face validity and predictive validity relative to the corresponding disorder in primates, and provides a cost-effective tool to evaluate novel antidyskinetic interventions. This article reviews the strategies that have been used to reproduce different motor complications of PD treatment in rodents, and comments on their range of applicability. (C) 2009 Elsevier Ltd. All rights reserved.