Neurotoxicity of the Meperidine Analogue N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on Brain Catecholamine Neurons in the Mouse

The effect of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) on central monoamine neurons in mice was investigated using histo- and biochemical techniques. NMPTP (2 X 10 mg/kg i.v.) produced a rapid and long-lasting reduction (-30%) of striatal dopamine, while the dopamine levels were only transiently reduced in mesencephalon and frontal cortex. HVA and DOPAC were initially markedly reduced (-50 to -70%) in striatum while a marked recovery was found in the chronic stage. NMPTP also induced a long-term reduction of noradrenaline in striatum and frontal cortex while 5-hydroxytryptamine and 5-HIAA levels were essentially unaltered. The data indicate a neurotoxic action of NMPTP on both dopamine and noradrenaline nerve terminals in mouse brain.