THE COMPETITIVE NMDA ANTAGONIST CPP PROTECTS SUBSTANTIA-NIGRA NEURONSFROM MPTP-INDUCED DEGENERATION IN PRIMATES

Degeneration of nigrostriatal dopaminergic neurons is the primary hist opathological feature of Parkinson's disease. The neurotoxin MPTP (1-m ethyl-4-phenyl-1,2,3,6-tetrahydropyridine) induces a neurological synd rome in man and non-human primates very similar to idiopathic Parkinso n's disease by selectively destroying dopaminergic nigrostriatal neuro ns. This gives rise to the hypothesis that Parkinson's disease may be caused by endogenous or environmental toxins. Endogenous excitatory am ino acids (EAAs) such as L-glutamate could be involved in neurodegener ative disorders including Parkinson's disease. We report in this study that the competitive NMDA antagonist CPP (+/-)-2-carboxypiperazin-4-y l)-propyl-1-phosphonic acid) protects nigral tyrosine hydroxylase (TH) positive neurons from degeneration induced by systemic treatment with MPTP in common marmosets. This indicates that EAAs are involved in th e pathophysiological cascade of MPTP-induced neuronal cell death and t hat EAA antagonists may offer a neuroprotective therapy for Parkinson' s disease.