Background: Oxidative stress and severe neuro-excitation have significant effects on pathogenesis of Parkinson’s disease and agents with antioxidant property can potentially prevent these effects. Herein we examined potential protective effects of melatonin as an antioxidant agent and memantine as an uncompetitive receptor of NMDA, on a model of Parkinson’s disease induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP).

  Materials and Methods: Male mice were divided into 8 groups with 7 mice in each group: saline, ethanol, melatonin, memantin, MPTP, melatonin+MPTP, memantin+ MPTP, melatonin+ memantin+ MPTP. All of agents were injected intraperitoneally once a day for 14 days before beam traversal test. Dopaminergic neurons of the Substantia Nigra Pars compacta (SNPC) were determined by immunohistochemical and were counted.

  Results: Melatonin improved notably movement dysfunction resulted of MPTP such as the number of errors, paces and the time of movement during behavioral test and also the counting of neurons of Substantia Nigra Pars Compacta. Memantin had a synergic effect on the most of improvements. However, the level of improvement and retrieval of signs was not as in saline and ethanol groups.

Conclusion: Melatonin especially together with memantine is able to prevent some of the MPTP-induced dysfunctions. However, the protective effects were not enogh, probably because of the amount of dose and the time of injection.