Protective effect of riluzole on MPTP-induced depletion of dopamine and its metabolite content in mice
| Autor: | Tsutomu Araki, T. Ido, Mitsunobu Matsubara, Y. Itoyama, T. Kumagai, Yutaka Imai |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Dopamine Dopamine Agents Striatum Receptors N-Methyl-D-Aspartate Biochemistry Neuroprotection Sodium Channels Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Internal medicine medicine Animals Neurons Riluzole Dose-Response Relationship Drug Chemistry MPTP Dopaminergic Brain Pargyline Corpus Striatum nervous system diseases Mice Inbred C57BL Neuroprotective Agents Endocrinology nervous system 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine 3 4-Dihydroxyphenylacetic Acid NMDA receptor Neurology (clinical) Dizocilpine Maleate medicine.drug |
| Zdroj: | Metabolic Brain Disease. 15:193-201 |
| ISSN: | 1573-7365 0885-7490 |
| DOI: | 10.1007/bf02674528 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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