Correlation between quantitative imaging and behavior in unilaterally 6-OHDA-lesioned rats
Correlation between quantitative imaging and behavior in unilaterally 6-OHDA-lesioned rats
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DOI：
10.1016/j.brainres.2005.09.055
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发表时间：
2005-12-07
期刊：
影响因子：
2.9
通讯作者：
Suhara, T
中科院分区：
文献类型：
--
作者：
Inaji, M;Okauchi, T;Suhara, T
我们评估了神经化学和功能改变的黑质纹状体多巴胺能系统在大鼠脑损伤与6-羟基多巴胺（6-OHDA），模型偏侧帕金森病（PD），通过使用三种不同的定量在体内和体外的方法之间的相关性。用不同剂量的6-ORDA单侧损伤大鼠进行两种类型的体内实验：（1）用甲基苯丙胺（MAP）或阿扑吗啡（APO）进行旋转行为研究;（2）用[C-11] PE 21（多巴胺转运蛋白的放射性配体）或[C-11]雷氯必利（多巴胺D2受体的放射性配体）进行正电子发射断层扫描（PET）研究。还使用相同的放射性配体进行了体外放射自显影研究。MAP或APO注射后的旋转次数随着6-OHDA剂量的增加而增加。6-OHDA注射后，[C-11] PE 21的体外和体内结合呈剂量依赖性降低，而[C-11]雷氯必利的结合呈剂量依赖性增加。MAP注射后的旋转次数与[C-11] PE 21的结合之间存在显著的负双曲线相关性。相反，APO注射后的旋转次数与[C-11]雷氯必利的结合率之间存在显著的正线性相关。这些结果有力地揭示了帕金森病动物模型中帕金森症状的分子药理学基础，并表明体内PET测量在评估突触前和突触后多巴胺能功能中的实用性和有效性。(C)2005 Elsevier B. V.保留所有权利。
We evaluated correlation between neurochemical and functional alterations of the nigrostriatal dopaminergic system in rat brains lesioned with 6-hydroxydopamine (6-OHDA), that model hemi-Parkinson's disease (PD), by using three different quantitative in vivo and in vitro methods. Rats unilaterally lesioned with different doses of 6-ORDA underwent two types of in vivo experiments: (1) a rotational behavioral study with methamphetamine (MAP) or apomorphine (APO); and (2) a positron emission tomography (PET) study with [C-11]PE21 (radioligand for dopamine transporters) or [C-11]raclopride (radioligand for dopamine D2 receptors). An in vitro autoradiographic study with the same radioligands was also conducted. The number of rotations after the MAP or APO injection increased with increased doses of 6-OHDA. The in vitro and in vivo binding of [C-11]PE21 dose-dependently decreased in response to the 6-OHDA injections, while that of [C-11]raclopride dose-dependently increased. There was a significant negative hyperbolic correlation between the number of rotations after MAP injection and the binding of [C-11]PE21. In contrast, there was a significant positive linear correlation between the number of rotations after APO injections and the binding of [C-11]raclopride. These results robustly reveal a molecular pharmacological basis of parkinsonian symptoms in animal models of PD, and indicate the utility and validity of in vivo PET measurements in assessing pre- and post-synaptic dopaminergic functions. (C) 2005 Elsevier B.V. All rights reserved.