Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / antagonists & inhibitors*
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3,4-Dihydroxyphenylacetic Acid / metabolism
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Animals
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Dizocilpine Maleate / pharmacology
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Dopamine / metabolism*
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Dose-Response Relationship, Drug
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Drug Interactions / physiology
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Excitatory Amino Acid Antagonists / pharmacology*
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Glutamic Acid / metabolism
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Homovanillic Acid / metabolism
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Immunohistochemistry
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Male
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Mice
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Mice, Inbred C57BL
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Neostriatum / drug effects*
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Neostriatum / metabolism
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Neostriatum / physiopathology
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Neurons / drug effects
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Neurons / metabolism
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Neuroprotective Agents / pharmacology*
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Parkinsonian Disorders / drug therapy*
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Parkinsonian Disorders / metabolism
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Parkinsonian Disorders / physiopathology
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Riluzole / pharmacology*
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Substantia Nigra / drug effects
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Substantia Nigra / metabolism
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Substantia Nigra / physiopathology
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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Tyrosine 3-Monooxygenase / metabolism
Substances
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Excitatory Amino Acid Antagonists
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Neuroprotective Agents
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3,4-Dihydroxyphenylacetic Acid
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Glutamic Acid
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Dizocilpine Maleate
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Riluzole
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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Tyrosine 3-Monooxygenase
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Dopamine
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Homovanillic Acid