Depletion of striatal dopamine by the N-oxide of 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP)

Y. S. Lau, Y. K. Fung, K. L. Trobough, J. R. Cashman, J. A. Wilson

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


The N-oxide of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the major metabolite found in vivo and excreted in urine after the parenteral administration of the neurotoxicant, MPTP. In mice (C57BL/6), stereotaxic injection of MPTP N-oxide (15 μg) into the neostriatum produced dopamine (DA) depletion similar to that caused by MPTP. The DA depleting effect of MPTP N-oxide was a direct action, whereas the action of MPTP was mediated by the generation of oxidative metabolites. In the mouse striatal synaptosomal preparation, MPTP, MPP+ and MPTP N-oxide all competed with [3H]DA at its uptake site. In addition, MPP+ and MPTP N-oxide promoted [3H]DA release. In contrast to MPTP and MPDP+, MPTP N-oxide did not alter the electrophysiologically recorded field potential in nigro-striatal slices. These observations suggest that MPTP N-oxide can directly cause the chemical depletion of striatal DA without modifying the characteristics of cortico- striate synaptic transmission.

Original languageEnglish (US)
Pages (from-to)189-200
Number of pages12
Issue number2
StatePublished - 1991


  • Dopamine Depletion
  • Dopamine Uptake and Release
  • MPP
  • MPTP
  • MPTP N-oxide
  • Neostriatal Transmission

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology


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