Modeling Parkinson’s disease in primates: the MPTP model

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate models of Parkinson’s disease (PD) reproduce most, although not all, of the clinical and pathological hallmarks of PD. The present contribution presents the possibilities offered by the MPTP monkey models of PD to readers with minimal knowledge of PD, emphasizing the diversity of species, route and regimen of administration, symptoms and pathological features. Readers would eventually find out that there is not a single MPTP monkey model of PD but instead MPTP monkey models of PD, each addressing a specific experimental need. Parkinson’s disease (PD) is a neurodegen-erative disorder whose cardinal manifesta-tions are due primarily to a profound deficit in brain dopamine. Several therapeutic strategies have been discovered to treat the symptoms of this neurological disorder, but, as of yet, none halts or retards the neurodegenerative process. In an attempt to shed light into the neurobiology of PD, a number of experimental models have been developed, especially during the last 25 years. In 1982, a cluster of young drug addicts came down with a clinical picture almost indis-tinguishable from PD after the self-administra-tion of a synthetic heroin analogue contaminated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The resemblance to PD was so strik-ing that researchers quickly tested this com-pound in various animal species and showed that MPTPadministration was able to reproduce most, but not all, of the clinical and pathological hallmarks of PD in monkey (Chiueh et al. 1984; Langston et al. 1984; Crossman et al. 1985; Dou-det et al. 1985) and, at least the degeneration of dopaminergic neurons in mice (Heikkila et al. 1984), but not in rats which were found to be re-sistant to this toxin (Chiueh et al. 1984). The aim of the present contribution is not to review recent data, but rather to present the possibilities offered by the MPTP monkey model of PD to readers with minimal knowl-edge of PD for them to be ready to start working on PD