Animal models of l-DOPA-induced dyskinesia: an update on the current options.
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Major limitations to the pharmacotherapy of Parkinson's disease (PD) are the motor complications resulting from l-DOPA treatment. Abnormal involuntary movements (dyskinesia) affect a majority of the patients after a few years of l-DOPA treatment and can become troublesome and debilitating. Once dyskinesia has debuted, an irreversible process seems to have occurred, and the movement disorder becomes almost impossible to eliminate with adjustments in peroral pharmacotherapy. There is a great need to find new pharmacological interventions for PD that will alleviate parkinsonian symptoms without inducing dyskinesia. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned non-human primate model is an excellent symptomatic model of PD and was the first model used to reproduce l-DOPA-induced dyskinesia experimentally. As it recapitulates the motor features of human dyskinesia, that is, chorea and dystonia, it is considered a reliable animal model to define novel therapies. Over the last decade, rodent models of l-DOPA-induced dyskinesia have been developed, having both face validity and predictive validity. These models have now become the first-line experimental tool for therapeutic screening purposes. The application of classical 6-hydroxydopamine (6-OHDA) lesion procedures to produce rodent models of dyskinesia has provided the field with more dynamic tools, since the versatility of toxin doses and injection coordinates allows for mimicking different stages of PD. This article will review models developed in non-human primate and rodents to reproduce motor complications induced by dopamine replacement therapy. The recent breakthroughs represented by mouse models and the relevance of rodents in relation to non-human primate models will be discussed. This article is part of a Special Issue entitled: Neuroscience Disease Models.
|Enheter & grupper|
Ämnesklassifikation (UKÄ) – OBLIGATORISK
|Status||Published - 2012|
|Peer review utförd||Ja|