ABSTRACT
INTRODUCTION The dopaminergic nervous system in brain has been the most-intensively studied of all the known neuronal phenotypes, owing in large part to the availability of neurotoxins able to produce selective destruction and thereby model Parkinson disease (PD) ( 1-3 ), attention-defi cit hyperactivity disorder (ADHD) ( 4-8 ), and Lesch-Nyhan syndrome ( 9-11 ). The fi rst available dopaminergic neurotoxin was 6-hydroxydopamine (6-OHDA), discovered before 1970 and used in more than 9000 published studies ( 3 , 11 , 12 ). Substituted AMPHs were similarly found to be neurotoxic to dopaminergic as well as serotoninergic nerves (13) . However, it was the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) that reinvigorated studies of the dopaminergic system, owing to its inadvertent use in the early 1980s by humans abusing drugs and its rapid (days) production of an irreversible parkinsonian state ( 14-16 ). MPTP is widely used to produce animal modeling of PD. Over the past 15 years the cytotoxin rotenone, a mitochondrial complex I inhibitor of oxidative phosphorylation, has been widely used chronically in low amount to model PD because this treatment results in the production of protein aggregates in brain similar to that accompanying human PD (17) . Most recently, MPTP administrated chronically in low amount has been shown to also result in the presence of protein aggregates in the brain of animal models of PD (18) .
