MPTP-Induced nigrostriatal injury in nonhuman primates

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced injury to dopaminergic neurons of the nigrostriatal pathways of nonhuman primates is an important model for Parkinsonism and, more recently, also for dystonia. In particular, the nonhuman primate model provides behavioral responses that closely mimic human Parkinsonism, including response to medication. This may reflect the close similarities between basal ganglia anatomy and pharmacology of nonhuman primates and humans. These advantages have led to the use of this model system to investigate pathophysiology of nigrostriatal denervation and to develop and test new therapeutic interventions. This chapter reviews the different methods of MPTP administration, the behavioral responses to MPTP, the pathophysiological consequences of this denervation, and the use of this model to investigate new treatments for Parkinsonism. Although MPTP administration in nonhuman primates provides a good behavioral, physiological, and pharmacological model of human idiopathic PD, several limitations must be considered. First, the etiology of this form of Parkinsonism, regardless of the timing of MPTP administration, is not the same as human PD. Therefore, investigators must carefully assess the purpose of the study before assuming that the use of MPTP-induced nigrostriatal injury in nonhuman primates is the proper model. Nevertheless, many important advances in understanding both Parkinsonism and dystonia are made with MPTP-treated nonhuman primates.