Kilbourn M R, Kuszpit K, Sherman P
Division of Nuclear Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Synapse. 2000 Mar 15;35(4):250-5. doi: 10.1002/(SICI)1098-2396(20000315)35:4<250::AID-SYN2>3.0.CO;2-S.
The dose- and time-dependent changes of in vivo radioligand binding to the neuronal membrane dopamine transporter (DAT) and vesicular monoamine transporter type 2 (VMAT2) were examined in mouse brain after MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) administrations. Regional brain distribution studies were done in male C57BL/6 mice using simultaneous injections of d-threo-[(3)H]methylphenidate (DAT) and (+)-alpha-[(11)C]dihydrotetrabenazine (VMAT2). Single (55 mg/kg i.p. ) or multiple (4 x 10 mg/kg i.p., 1-hour intervals) administration of MPTP caused significant reductions in [(3)H]methylphenidate and [(11)C]dihydrotetrabenazine specific striatal binding, measured 14 days later. The single high dose of MPTP produced greater losses of [(11)C]dihydrotetrabenazine binding than did the multiple MPTP dosing regimen. Using the single high dose of MPTP, changes of in vivo binding of the two radioligands were determined at 1, 3, and 14 days after neurotoxin injection. At 1 day, there are large losses of [(3)H]methylphenidate binding (DAT) but no changes in [(11)C]dihydrotetrabenazine binding to the VMAT2 site in the striatum. At 3 and 14 days, there were >50% losses of binding of both bot radioligands, but significantly (P < 0.001) greater losses of VMAT2 binding of [(11)C]dihydrotetrabenazine. These studies indicate that the losses of the neuronal membrane and vesicular transporters are not always equal, and do not occur in the same time frame, after administration of the neurotoxin MPTP.
在给予1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）后，检测了小鼠脑内放射性配体与神经元膜多巴胺转运体（DAT）和2型囊泡单胺转运体（VMAT2）结合的剂量和时间依赖性变化。使用同时注射d-苏式-[(3)H]哌醋甲酯（DAT）和(+)-α-[(11)C]二氢丁苯那嗪（VMAT2）的方法，对雄性C57BL/6小鼠进行了脑区分布研究。单次（腹腔注射55mg/kg）或多次（4×10mg/kg腹腔注射，间隔1小时）给予MPTP后，14天后检测到[(3)H]哌醋甲酯和[(11)C]二氢丁苯那嗪在纹状体的特异性结合显著降低。单次高剂量的MPTP比多次MPTP给药方案导致[(11)C]二氢丁苯那嗪结合的损失更大。使用单次高剂量的MPTP，在神经毒素注射后1、3和14天测定了两种放射性配体的体内结合变化。在第1天，[(3)H]哌醋甲酯结合（DAT）有大量损失，但纹状体中[(11)C]二氢丁苯那嗪与VMAT2位点的结合没有变化。在第3天和第14天，两种放射性配体的结合损失均>50%，但[(11)C]二氢丁苯那嗪与VMAT2的结合损失显著（P<0.001）更大。这些研究表明，在给予神经毒素MPTP后，神经元膜和囊泡转运体的损失并不总是相等，且发生的时间框架也不同。
