Fuller R W, Hemrick-Luecke S K
Res Commun Chem Pathol Pharmacol. 1985 Apr;48(1):17-25.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) given in 4 daily s.c. injections to mice resulted in marked depletion of striatal dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) 1 week after the last dose. Pretreatment of mice with alpha-methyltyrosine or Ro 4-1284 to deplete dopamine prior to MPTP injection did not prevent these effects of MPTP, nor did pretreatment with haloperidol, a dopamine receptor antagonist. The depletion of striatal dopamine by MPTP in mice therefore differs from the persistent depletion of striatal dopamine by amphetamine in iprindole-treated rats, which is prevented by pretreatment with either alpha-methyltyrosine or haloperidol. The depletion of dopamine, DOPAC and HVA in mouse striatum by MPTP was totally prevented by pretreatment with amfonelic acid, an inhibitor of dopamine uptake. This finding suggests that these effects of MPTP, like those of amphetamine in iprindole-treated rats, are dependent upon a functional transport system into the dopamine neuron.
对小鼠每日皮下注射4次1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP），在末次给药1周后可导致纹状体多巴胺、3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）显著耗竭。在注射MPTP前用α-甲基酪氨酸或Ro 4-1284使多巴胺耗竭对小鼠进行预处理，并不能预防MPTP的这些作用，多巴胺受体拮抗剂氟哌啶醇预处理也不能预防。因此，MPTP导致小鼠纹状体多巴胺耗竭不同于安非他明在茚满二酮处理的大鼠中导致的纹状体多巴胺持续耗竭，后者可通过α-甲基酪氨酸或氟哌啶醇预处理来预防。MPTP导致小鼠纹状体多巴胺、DOPAC和HVA耗竭可通过多巴胺摄取抑制剂氨苯利酸预处理完全预防。这一发现表明，MPTP的这些作用，如同安非他明在茚满二酮处理的大鼠中的作用一样，依赖于进入多巴胺能神经元的功能性转运系统。
