Experimental models of Parkinson's disease: Insights from many models

Toxin-induced and genetic experimental models have been invaluable in inves tigating idiopathic Parkinson's disease (PD),The neurotoxins-reserpine, 6-h ydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP ), and methamphetamine-have been used to develop parkinsonian models in a w ide variety of species. Both 6-OHDA and MPTP can replicate the neurochemica l, morphologic, and behavioral changes seen in human disease. The unilatera l 6-OHDA rat model is an excellent model for testing and determining modes of act;ion of new pharmacologic compounds. The nonhuman primate MPTP-induce d parkinsonian model has behavioral features that best approximate idiopath ic PD, These induced and genetic models have been used to study the pathoph ysiology of the degenerating nigrostriatal system and to evaluate novel the rapeutic strategies. Important differences within these models provide insi ghts into various aspects of the dopaminergic phenotype and its role as a t arget in disease. These models provide an avenue to evaluate many anti-park insonian compounds, such as levodopa, which was first evaluated in an anima l model and is the gold standard of parkinsonian treatment today.