Namura I, Douillet P, Sun C J, Pert A, Cohen R M, Chiueh C C
Eur J Pharmacol. 1987 Apr 7;136(1):31-7. doi: 10.1016/0014-2999(87)90775-8.
1-Methyl-4-phenylpyridine (MPP+) is an oxidative metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP). MPP+ produced local cell death when injected directly into substantia nigra compacta, locus coeruleus, or dorsal and median raphe nuclei of rats. Corresponding significant decreases in dopamine, serotonin and norepinephrine levels were observed in the terminal areas. These observations indicate that MPP+ is a non-selective neurotoxin which causes lesions not only in dopaminergic neurons but also in noradrenergic and serotonergic systems following intracranial administration. Selective lesioning of these monoaminergic systems could only be achieved by a stereotaxic injection of MPP+ into specific brain regions containing monoamine neurons.
1-甲基-4-苯基吡啶(MPP+)是1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)的氧化代谢产物。将MPP+直接注射到大鼠黑质致密部、蓝斑或背侧和中缝核时会导致局部细胞死亡。在终末区域观察到多巴胺、5-羟色胺和去甲肾上腺素水平相应显著下降。这些观察结果表明,MPP+是一种非选择性神经毒素,颅内给药后不仅会导致多巴胺能神经元损伤,还会导致去甲肾上腺素能和5-羟色胺能系统损伤。只有通过立体定向将MPP+注射到含有单胺能神经元的特定脑区,才能实现这些单胺能系统的选择性损伤。