Experimental Models of l-DOPA-Induced Dyskinesia

Strategies to avoid or minimize dyskinesia and other motor complications of chronic dopamine replacement therapy in Parkinson's disease (PD) remain a significant unmet clinical need. As such, the refinement and development of animal models with which to delineate the underlying molecular mechanisms of dyskinesia and to find effective treatment paradigms remain as necessary as ever. Toxin-based models including the MPTP-lesioned primate and the 6-hydroxydopamine (6-OHDA) lesioned rodent continue to form the bedrock of current l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesia modeling approaches. This chapter reviews these models, illustrating their origins, application and strengths as well as problems that accompany their use. We also describe new methodologies that, although still in their infancy, may offer powerful future alternatives by which to better model this debilitating complication of current PD treatment.