In vivo protection of striatum from MPP + neurotoxicity by [formula omitted] antagonists

Abstract

The present study was designed to assess by microdialysis whether N- methyl- d-aspartate (NMDA) non-competitive receptor antagonist, MK-801, is able to protect dopaminergic neurons against 1-methyl-4-phenylpyridinium ion (MPP +) neurotoxicity. An intraperitoneal injection of MK-801, 10 μmol/kg, half an hour before striatal MPP +, 10 mM, perfusion did not protect against its neurotoxicity. Afterwards, rats received an intraperitoneal injection of MK-801 every 4 h, during 24 h. Under these conditions, one day after MPP + perfusion, DA basal extracellular levels were close to the detection limit of our HPLC equipment in both control and MK-801 treated rats. 3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) basal output were lower in the former than in the latter rats. A second MPP + perfusion statistically increased extracellular levels of DA and decreased DOPAC and HVA output in both groups of rats. However, the increase in extracellular DA overflow was higher in MK-801 treated rats than in the control group, indicating a higher number of surviving dopaminergic terminals. These results suggest that MK-801 is not able to protect against the primary direct neutoxic action of MPP +, but a second MPP + neurotoxic action mediated by excitatory amino acids could be partially prevented by MK-801.