THE N-METHYL-D-ASPARTATE ANTAGONIST MK-801 FAILS TO PROTECT DOPAMINERGIC-NEURONS FROM 1-METHYL-4-PHENYLPYRIDINIUM TOXICITY INVITRO

Recent reports suggest that NMDA receptor antagonists when administere d in vivo can protect dopaminergic neurons from the toxic actions of M PP+. In the present study the possible neuroprotective effects against MPP+ toxicity of the noncompetitive NMDA receptor antagonist MK-801 w as studied in primary cultures of fetal rat mesencephalic dopamine neu rons. MK-801 failed to protect dopaminergic neurons from MPP+ toxicity at concentrations that completely block NMDA-induced toxicity of thes e 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 cyclohexim ide. Our findings suggest that the toxic effects of MPP+ on dopaminerg ic neurons are not mediated through a direct interaction with the NMDA subtype of glutamate receptor.