Protective effect of riluzole on MPTP-induced depletion of dopamine and its metabolite content in mice

T. Araki, T. Kumagai, M. Matsubara, T. Ido, Y. Imai, Y. Itoyama

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

The neuroprotective effects of riluzole (2-amino-6-trifluoromethoxy benzothiazole), a Na+ channel blocker with antiglutamatergic activity, MK-801, a blocker of N-methyl-D-aspartate (NMDA) receptors and monoamine oxidase (MAO) inhibitor pargyline were compared in the model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced depletion of dopamine and its metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) levels in mice. The mice received four intraperitoneal injections of MPTP (10 mg/kg) at 1-hr intervals and then the brains were analyzed at 1, 3 and 7 days after the treatments. Dopamine and DOPAC levels were significantly decreased in the striatum from 1 day after MPTP treatments. A severe depletion in dopamine and DOPAC levels was found in the striatum 3 and 7 days after MPTP treatments. Riluzole dose-dependently antagonized the MPTP-induced decrease in dopamine and DOPAC levels in the striatum. Pargyline also protected against MPTP-induced decrease in dopamine levels in the striatum. However, this drug showed no significant change in the striatal DOPAC levels. On the other hand, MK-801 failed to protect against MPTP-induced decrease in dopamine levels in the striatum. However, MK-801 reversed the MPTP-induced decrease in DOPAC levels. These results suggest that riluzole can protect against MPTP-induced striatal dopamine and DOPAC depletion in mice. This protective effect may be caused by inactivation of voltage-dependent Na+ channels by riluzole. Furthermore, the present study suggests that the activation of NMDA receptors does not mainly contribute to MPTP-induced neurodegeneration, whereas MAO, especially MAO type B(MAO-B) plays a crucial role in MPTP-induced degeneration of the nigrostriatal dopaminergic neuronal pathway.

Original languageEnglish
Pages (from-to)193-201
Number of pages9
JournalMetabolic Brain Disease
Volume15
Issue number3
DOIs
Publication statusPublished - 2000 Dec 1

Keywords

  • Dopamine
  • MK-801
  • MPTP
  • Mice
  • Pargyline
  • Riluzole

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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