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注意缺陷多动障碍中多巴胺紧张性释放减弱及相位性释放增强

Attenuated Tonic and Enhanced Phasic Release of Dopamine in Attention Deficit Hyperactivity Disorder.

作者信息

Badgaiyan Rajendra D, Sinha Sampada, Sajjad Munawwar, Wack David S

机构信息

Molecular and Functional Imaging Laboratory, Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, United States of America; Neuromodulation Program, University of Minnesota Twin City Campus, Minneapolis, Minnesota, United States of America; Laboratory of Advanced Radiochemistry, University of Minnesota Twin City Campus, Minneapolis, Minnesota, United States of America.

Molecular and Functional Imaging Laboratory, Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, United States of America.

出版信息

PLoS One. 2015 Sep 30;10(9):e0137326. doi: 10.1371/journal.pone.0137326. eCollection 2015.

Abstract

It is unclear whether attention deficit hyperactive disorder (ADHD) is a hypodopaminergic or hyperdopaminergic condition. Different sets of data suggest either hyperactive or hypoactive dopamine system. Since indirect methods used in earlier studies have arrived at contradictory conclusions, we directly measured the tonic and phasic release of dopamine in ADHD volunteers. The tonic release in ADHD and healthy control volunteers was measured and compared using dynamic molecular imaging technique. The phasic release during performance of Eriksen's flanker task was measured in the two groups using single scan dynamic molecular imaging technique. In these experiments volunteers were positioned in a positron emission tomography (PET) camera and administered a dopamine receptor ligand (11)C-raclopride intravenously. After the injection PET data were acquired dynamically while volunteers either stayed still (tonic release experiments) or performed the flanker task (phasic release experiments). PET data were analyzed to measure dynamic changes in ligand binding potential (BP) and other receptor kinetic parameters. The analysis revealed that at rest the ligand BP was significantly higher in the right caudate of ADHD volunteers suggesting reduced tonic release. During task performance significantly lower ligand BP was observed in the same area, indicating increased phasic release. In ADHD tonic release of dopamine is attenuated and the phasic release is enhanced in the right caudate. By characterizing the nature of dysregulated dopamine neurotransmission in ADHD, the results explain earlier findings of reduced or increased dopaminergic activity.

摘要

注意力缺陷多动障碍(ADHD)究竟是多巴胺能功能减退还是亢进尚不清楚。不同的数据集表明多巴胺系统存在活动亢进或减退的情况。由于早期研究中使用的间接方法得出了相互矛盾的结论,我们直接测量了ADHD志愿者中多巴胺的紧张性和相位性释放。使用动态分子成像技术测量并比较了ADHD志愿者和健康对照志愿者的紧张性释放。在两组中使用单次扫描动态分子成像技术测量了埃里克森侧翼任务执行过程中的相位性释放。在这些实验中,志愿者被安置在正电子发射断层扫描(PET)相机中,并静脉注射多巴胺受体配体(11)C-雷氯必利。注射后,在志愿者静止不动(紧张性释放实验)或执行侧翼任务(相位性释放实验)时动态采集PET数据。分析PET数据以测量配体结合潜能(BP)和其他受体动力学参数的动态变化。分析显示,在静息状态下,ADHD志愿者右侧尾状核的配体BP显著更高,表明紧张性释放减少。在任务执行过程中,在同一区域观察到配体BP显著更低,表明相位性释放增加。在ADHD中,右侧尾状核的多巴胺紧张性释放减弱,相位性释放增强。通过描述ADHD中多巴胺神经传递失调的性质,这些结果解释了早期多巴胺能活性降低或增加的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5286/4589406/4f897610ee9c/pone.0137326.g001.jpg

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