Momosaki Sotaro, Ito Miwa, Yamato Hiroko, Iimori Hitoshi, Sumiyoshi Hirokazu, Morimoto Kenji, Imamoto Natsumi, Watabe Tadashi, Shimosegawa Eku, Hatazawa Jun, Abe Kohji
1 Department of Drug Metabolism & Pharmacokinetics, Shionogi & Co., Ltd., Osaka, Japan.
2 Department of Applied Chemistry & Analysis, Shionogi & Co., Ltd., Osaka, Japan.
J Cereb Blood Flow Metab. 2017 Feb;37(2):605-613. doi: 10.1177/0271678X16635183. Epub 2016 Jul 20.
The changes in the availability of striatal dopamine transporter and dopamine D2 receptor after mild focal ischemia in rats were measured using a small animal positron emission tomography system. Mild focal ischemia was induced by 20-minute middle cerebral artery occlusion. [C]PE2I binding to dopamine transporter was transiently increased on the ipsilateral side of the striatum at 2 days after middle cerebral artery occlusion. On day 7 and 14 after middle cerebral artery occlusion, [C]PE2I binding levels were decreased. In contrast, [C]raclopride binding to dopamine D2 receptor in the ipsilateral striatum had not changed at 2 days after middle cerebral artery occlusion. [C]Raclopride binding was significantly decreased on the ischemic side of the striatum at 7 and 14 days after middle cerebral artery occlusion. Moreover, on day 1 and 2 after middle cerebral artery occlusion, significant circling behavior to the contralateral direction was induced by amphetamine challenge. This behavior disappeared at 7 days after middle cerebral artery occlusion. At 14 days, circling behavior to the ipsilateral direction (middle cerebral artery occlusion side) was significantly increased, and that to the contralateral direction also appeared again. The present study suggested that amphetamine-induced circling behavior indicated striatal dopaminergic alterations and that dopamine transporter and dopamine D2 receptor binding could be key markers for predicting motor dysfunction after mild focal ischemia.
使用小动物正电子发射断层扫描系统测量大鼠轻度局灶性缺血后纹状体多巴胺转运体和多巴胺D2受体可用性的变化。通过大脑中动脉闭塞20分钟诱导轻度局灶性缺血。大脑中动脉闭塞后2天，纹状体同侧[C]PE2I与多巴胺转运体的结合短暂增加。大脑中动脉闭塞后第7天和第14天，[C]PE2I结合水平降低。相比之下，大脑中动脉闭塞后2天，同侧纹状体中[C]雷氯必利与多巴胺D2受体的结合没有变化。大脑中动脉闭塞后第7天和第14天，纹状体缺血侧[C]雷氯必利结合显著降低。此外，大脑中动脉闭塞后第1天和第2天，苯丙胺激发诱导了向对侧方向的显著转圈行为。这种行为在大脑中动脉闭塞后7天消失。在第14天，向同侧方向（大脑中动脉闭塞侧）的转圈行为显著增加，向对侧方向的转圈行为也再次出现。本研究表明，苯丙胺诱导的转圈行为表明纹状体多巴胺能改变，多巴胺转运体和多巴胺D2受体结合可能是预测轻度局灶性缺血后运动功能障碍的关键标志物。
