Elsworth J D, Deutch A Y, Redmond D E, Sladek J R, Roth R H
Brain Res. 1987 Jul 14;415(2):293-9. doi: 10.1016/0006-8993(87)90211-3.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration is able to produce nigrostriatal damage and motor disabilities in primates similar to those seen in Parkinson's disease. Two months after MPTP treatment in African Green monkeys, significant depletions of dopamine (DA) and/or homovanillic acid (HVA) were found in the dorsal ventral tegmental area, and septum, but not in the ventral part of the ventral tegmental area or nucleus accumbens. However, DA losses were greater at all examined sites in the striatum. In putamen and caudate nucleus the decreases in DA and HVA appeared more marked dorsolaterally than ventromedially. After MPTP treatment the ratio HVA/DA was elevated in the septum and all striatal regions; in the striatum the increases in ratio were greater in the dorsolateral than in the ventromedial samples. NE concentration was not significantly altered by MPTP in the mesolimbic system. In control animals the HVA concentration and the ratio HVA/DA were higher in the putamen than in the caudate nucleus. A longitudinal study showed that CSF HVA and 3-methoxy-4-hydroxyphenylglycol were reduced by MPTP and remained below baseline level for 12 months after MPTP treatment. This biochemical study indicates that in the monkey MPTP is able to induce selective damage within both the nigrostriatal and mesolimbic DA systems.
给予1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）能够在灵长类动物中产生黑质纹状体损伤和运动障碍，类似于帕金森病中所见的情况。在非洲绿猴接受MPTP治疗两个月后，在背侧腹侧被盖区和隔区发现多巴胺（DA）和/或高香草酸（HVA）显著减少，但在腹侧被盖区腹侧部分或伏隔核中未发现减少。然而，纹状体中所有检查部位的DA损失更大。在壳核和尾状核中，DA和HVA的减少在背外侧比腹内侧更明显。MPTP治疗后，隔区和所有纹状体区域的HVA/DA比值升高；在纹状体中，背外侧样本的比值升高幅度大于腹内侧样本。MPTP对中脑边缘系统中的去甲肾上腺素（NE）浓度没有显著影响。在对照动物中，壳核中的HVA浓度和HVA/DA比值高于尾状核。一项纵向研究表明，MPTP可降低脑脊液中的HVA和3-甲氧基-4-羟基苯乙二醇水平，且在MPTP治疗后12个月内一直低于基线水平。这项生化研究表明，在猴子中，MPTP能够在黑质纹状体和中脑边缘多巴胺系统中诱导选择性损伤。
