Christian Bradley T, Vandehey Nicholas T, Fox Andrew S, Murali Dhanabalan, Oakes Terrence R, Converse Alex K, Nickles Robert J, Shelton Steve E, Davidson Richard J, Kalin Ned H
Department of Psychiatry, University of Wisconsin-Madison, USA; Department of Medical Physics, University of Wisconsin-Madison, USA.
Neuroimage. 2009 Feb 15;44(4):1334-44. doi: 10.1016/j.neuroimage.2008.10.020. Epub 2008 Oct 29.
PET imaging of the neuroreceptor systems in the brain has earned a prominent role in studying normal development, neuropsychiatric illness and developing targeted drugs. The dopaminergic system is of particular interest due to its role in the development of cognitive function and mood as well as its suspected involvement in neuropsychiatric illness. Nonhuman primate animal models provide a valuable resource for relating neurochemical changes to behavior. To facilitate comparison within and between primate models, we report in vivo D2/D3 binding in a large cohort of adolescent rhesus monkeys.
In this work, the in vivo D2/D3 dopamine receptor availability was measured in a cohort of 33 rhesus monkeys in the adolescent stage of development (3.2-5.3 years). Both striatal and extrastriatal D2/D3 binding were measured using [F-18]fallypride with a high resolution small animal PET scanner. The distribution volume ratio (DVR) was measured for all subjects and group comparisons of D2/D3 binding among the cohort were made based on age and sex. Because two sequential studies were acquired from a single [F-18]fallypride batch, the effect of competing (unlabeled) ligand mass was also investigated.
Among this cohort, the rank order of regional D2/D3 receptor binding did not vary from previous studies with adult rhesus monkeys, with: putamen>caudate>ventral striatum>amygdala approximately substantia nigra>medial dorsal thalamus>lateral temporal cortex approximately frontal cortex. The DVR coefficient of variation ranged from 14%-26%, with the greatest variance seen in the head of the caudate. There were significant sex differences in [F-18]fallypride kinetics in the pituitary gland, but this was not observed for regions within the blood-brain barrier. Furthermore, no regions in the brain showed significant sex or age related differences in DVR within this small age range. Based on a wide range of injected fallypride mass across the cohort, significant competition effects could only be detected in the substantia nigra, thalamus, and frontal cortex, and were not evident above intersubject variability in all other regions.
These data represent the first report of large cohort in vivo D2/D3 dopamine whole brain binding in the adolescent brain and will serve as a valuable comparison for understanding dopamine changes during this critical time of development and provide a framework for creating a dopaminergic biochemical atlas for the rhesus monkey.
大脑神经受体系统的正电子发射断层扫描（PET）成像在研究正常发育、神经精神疾病以及开发靶向药物方面发挥了重要作用。多巴胺能系统因其在认知功能和情绪发展中的作用以及涉嫌参与神经精神疾病而备受关注。非人灵长类动物模型为将神经化学变化与行为联系起来提供了宝贵资源。为便于在灵长类模型内部和之间进行比较，我们报告了一大群青春期恒河猴体内D2/D3结合情况。
在这项研究中，使用[F-18]氟哌利多和高分辨率小动物PET扫描仪，对33只处于青春期发育阶段（3.2 - 5.3岁）的恒河猴进行了体内D2/D3多巴胺受体可用性测量。测量了纹状体和纹状体以外区域的D2/D3结合情况。对所有受试者测量了分布体积比（DVR），并根据年龄和性别对该队列中D2/D3结合情况进行了组间比较。由于从一批[F-18]氟哌利多中获取了两项连续研究，还研究了竞争（未标记）配体质量的影响。
在这个队列中，区域D2/D3受体结合的排序与之前对成年恒河猴的研究一致，即：壳核>尾状核>腹侧纹状体>杏仁核≈黑质>背内侧丘脑>颞叶外侧皮质≈额叶皮质。DVR变异系数在14% - 26%之间，尾状核头部的变异最大。垂体中[F-18]氟哌利多动力学存在显著性别差异，但在血脑屏障内的区域未观察到这种差异。此外，在这个小年龄范围内，大脑中没有区域在DVR方面表现出显著的性别或年龄相关差异。基于该队列中广泛的氟哌利多注射质量范围，仅在黑质、丘脑和额叶皮质中检测到显著的竞争效应，在所有其他区域中，这种效应在个体间变异性之上并不明显。
这些数据代表了青春期大脑中一大群体内D2/D3多巴胺全脑结合的首次报告，将为理解这一关键发育时期的多巴胺变化提供有价值的比较，并为创建恒河猴多巴胺能生化图谱提供框架。
