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The N-Methyl-D-Aspartate Antagonist MK-801 Fails to Protect Dopaminergic Neurons from 1-Methyl-4- Phenylpyridinium Toxicity In Vitro
Authors:Francoise Finiels-Marlier  Ann M Marini  Pat Williams  Steven M Paul
Institution:Section on Molecular Pharmacology, Clinical Neuroscience Branch, National Institute of Mental Health, Bethesda, Maryland, U.S.A.
Abstract:Abstract: Recent reports suggest that NMDA receptor antagonists when administered in vivo can protect dopaminergic neurons from the toxic actions of MPP+. In the present study the possible neuroprotective effects against MPP+ toxicity of the noncompetitive NMDA receptor antagonist MK-801 was studied in primary cultures of fetal rat mesencephalic dopamine neurons. MK-801 failed to protect dopaminergic neurons from MPP+ toxicity at concentrations that completely block NMDA-induced toxicity of these same neurons. In contrast to work carried out in cerebellar granule cells, MPP+ toxicity of mesencephalic dopamine neurons was unaffected by preexposure to subtoxic concentrations of either NMDA or cycloheximide. Our findings suggest that the toxic effects of MPP+ on dopaminergic neurons are not mediated through a direct interaction with the NMDA subtype of glutamate receptor.
Keywords:1-Methyl-4-phenylpyridinium  Mesencephalic cultures  Dopaminergic neurons  N'-Methyl-D-aspartate receptor  MK-801
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