Investigation of Basal Ganglia Function and Intrinsic Dopamine Release by Positron Emission Tomography

为了研究黑质纹状体多巴胺系统在非学习的复杂运动任务（如写作）中的作用，我们用^<13>C-raclopride （RAC）和PET测量了人脑内源性多巴胺的释放。我们研究了6名右撇子健康志愿者（年龄22.0±1.7岁）。静脉注射RAC后，进行60分钟动态扫描。在两种不同条件下，每位受试者在同一天（扫描间隔145.0±35.2分钟）参加2次RAC-PET；书写时和休息时保持平衡。在写作条件下，受试者被要求用右手在电脑控制的书写板上用钢笔工具尽可能快地口述句子。在休息状态下，受试者被要求在不动的情况下观看显示器。根据两种不同条件下PAC结合电位（BP）的差异，基于占用模型间接估计内源性多巴胺释放量。同样的被试也参与了H_<2>^<15>的O-PET测试，从区域脑血流变化的角度来评估任务的区域脑激活。H_<2>^<15 >50 - pet研究写作任务时，左纹状体明显激活。在同一区域，听写任务显著降低RAC的结合电位，因此，认为任务加速了多巴胺的内在释放。激活区域位于壳核的腹尾部，我们之前报道过与基底神经节中某个组织的手区相对应。实验结果证明了RAC-PET间接测量生理状态下多巴胺释放量的可行性。我们的研究结果是第一个通过熟练的自主运动激活多巴胺能神经元的报告。

To investigate the role of nigrostriatal dopamine system in performing a skilled complex motor task without leaning such as writing, we measured endogenous dopamine release in human brain with ^<13>C-raclopride (RAC) and PET.We studied six right-handed healthy volunteers (ages 22.0±1.7 years). After an intravenous injection of RAC, a 60 minites dynamic scan was performed. Each subject participated in RAC-PET twice on the same day (scan interval 145.0±35.2 minutes) under two different conditions ; during hand writing and at rest in balanced order. In the writing condition, the subjects was asked to dictate sentences as quick as possible on a computer-controlled writing pad with pen tool using their right hand. In resting condition, the subject was asked to watch the display without any movement. Endgeneous dopamine release was estimated indirectly based on the occupancy model, from the difference of the binding potential (BP) of PAC in two different conditions. The same subjects also participated in H_<2>^<15>O-PET with the same paradigm to evaluate the regional cerebral activation with the task in terms of regional cerebral blood flow change.The left striatum was activated significantly with H_<2>^<15>5O-PET study with writing task. In the same region, the binding potentials of RAC was significantly reduced by dictation task, thus, the intrinsic dopamine release was considered to be accelerated by the task. The activated region located in the ventro-caudal portion of the putamen which we previosly reported to be corresponding to hand area in the sometotopic organization in the basal ganglia. This result demonstrated the ability of indirect measurement method of intrinsic dopamine release by RAC-PET in physiological condition. Our results are the first report of activation of dopaminergic neurons by a skilled voluntary monements.