Wallace R A, Boldry R, Schmittgen T, Miller D, Uretsky N
Life Sci. 1984 Jul 16;35(3):285-91. doi: 10.1016/0024-3205(84)90112-7.
The effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was studied on dopamine (DA), norepinephrine (NE), serotonin (5HT) and gamma-aminobutyric acid (GABA) neurons in mouse brain and on NE neurons of mouse heart. MPTP (45 mg/kg) was administered s.c. to mice twice daily for 2 consecutive days. This dosage regimen produced a decrease in the forebrain concentrations of DA and NE at 7 and 20 days after injection. In contrast, the forebrain concentrations of 5HT and GABA were not significantly decreased at either time. MPTP administration also produced a marked decrease in the uptake of 3H-DA into striatal slices and 3H-NE into cerebral cortical slices. In contrast, the uptake of 3H-NE into hypothalamic slices and the uptake of 3H-5HT into slices from several brain regions were not altered. MPTP initially reduced the concentration of NE in the heart, but unlike the persistent decreases in the forebrain concentrations of NE and DA, the NE concentration in the heart returned to control levels at approximately 20 days after MPTP administration. These results, showing that MPTP can produce a long lasting and selective decrease in the forebrain concentrations of NE and DA and in the uptake of radioactive DA and NE into brain slices, suggest that MPTP can cause the destruction of catecholamine neurons in mouse brain. In contrast, MPTP administration does not appear to produce long term changes in either 5HT or GABA neurons.
研究了1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）对小鼠脑内多巴胺（DA）、去甲肾上腺素（NE）、5-羟色胺（5HT）和γ-氨基丁酸（GABA）神经元以及小鼠心脏NE神经元的影响。将MPTP（45mg/kg）皮下注射给小鼠，每天2次，连续2天。这种给药方案导致注射后7天和20天时前脑DA和NE浓度降低。相比之下，5HT和GABA的前脑浓度在这两个时间点均未显著降低。给予MPTP还导致纹状体切片对3H-DA的摄取以及大脑皮质切片对3H-NE的摄取显著降低。相比之下，下丘脑切片对3H-NE的摄取以及几个脑区切片对3H-5HT的摄取未发生改变。MPTP最初降低了心脏中NE的浓度，但与前脑NE和DA浓度的持续降低不同，MPTP给药后约20天时心脏中NE浓度恢复到对照水平。这些结果表明，MPTP可使前脑NE和DA浓度以及放射性DA和NE进入脑切片的摄取产生长期且选择性的降低，提示MPTP可导致小鼠脑内儿茶酚胺神经元的破坏。相比之下，给予MPTP似乎不会对5HT或GABA神经元产生长期影响。
