Neuroprotective effect of riluzole in MPTP-treated mice

Tsutomu Araki, Toshihiko Kumagai, Katsuyuki Tanaka, Mitsunobu Matsubara, Hiroyuki Kato, Yasuto Itoyama, Yutaka Imai

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)


The neuroprotective effects of riluzole, a Na+ channel blocker with antiglutamatergic activity, and MK-801, a blocker of N-methyl-D-aspartate (NMDA) receptors, were compared in the model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced depletion of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in mice. The mice were injected intraperitoneally (i.p.) with four administrations of MPTP (10 mg/kg) at 1 h intervals and then the brains were analyzed 1, 3 and 7 days after the treatment. Dopamine and DOPAC levels were significantly decreased in the striatum from 1 day after MPTP treatment. A severe depletion in dopamine and DOPAC levels was found in the striatum 3 and 7 days after MPTP treatment. Riluzole antagonized the MPTP-induced decrease in dopamine, DOPAC and HVA levels in the striatum. On the other hand, MK-801 prevented the MPTP-induced decrease in DOPAC levels, but not in dopamine levels in the striatum. An immunohistochemical study indicated that riluzole can protect against MPTP-induced neuronal damage in the substantia nigra. These results suggest that riluzole is effective against MPTP-induced neurodegeneration of the nigrostriatal dopaminergic neuronal pathway.

Original languageEnglish
Pages (from-to)176-181
Number of pages6
JournalBrain research
Issue number1-2
Publication statusPublished - 2001 Nov 9


  • Dopamine
  • Immunohistochemistry
  • MK-801
  • MPTP
  • Mice
  • Parkinson's disease
  • Riluzole
  • Striatum

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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