Riluzole protects against MPTP induced dopamine and DOPAC depletion in mice

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

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated the neuroprotective effects of riluzole, a Na+ channel blocker with antiglutamatergic activity, MK-801, a blocker of N-methyl-D-aspartate (NMDA) receptors, monoamine oxidase (MAO) inhibitor parygline and MAO type-A (MAO-A) selective inhibitor clorgyline in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. The mice received four intraperitoneal injections of MPTP (10 mg/kg) at 1h intervals and then the brains were analyzed at 1,3 and 7 days after MPTP treatments. Dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) levels were significantly decreased in the striatum from 1 day after MPTP treatments. Thereafter, a severe depletion in dopamine and DOPAC levels was found in the striatum 3 and 7 days after MPTP treatments. Therefore, the evaluation of each compound was performed 3 days after MPTP treatments. Riluzole dose dependently antagonized the MPTP-induced decrease in dopamine and DOPAC levels in the striatum of mice. Pargyline and clorgyline also protected against MPTP-induced decrease in dopamine levels in the striatum of mice. However, these drugs showed no significantly change in the striatal DOPAC levels in MPTP-induced decrease in dopamine levels in the striatum of mice. 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 NMDA receptors are not mainly involved in mediating 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. These findings demonstrate that riluzole as well as MAO inhibitor may be useful in the treatment of Parkinson's diseases.

Original languageEnglish
Pages (from-to)157-172
Number of pages16
JournalBiogenic Amines
Volume16
Issue number2
Publication statusPublished - 2001 Jun 21

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

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