PET IMAGING OF EXTRASTRIATAL DOPAMINE LEVELS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究建议开发新的方法来测量D-苯丙胺诱导的多巴胺(DA)的释放和人类丘脑、边缘区、黑质和皮质中DA的细胞外基线水平。大量文献表明，这些区域的多巴胺能神经传递与精神分裂症、精神刺激性药物滥用和注意缺陷障碍的病理生理密切相关。目前，还没有测量这些区域DA释放或基线细胞外DA水平的方法。我们已经开发了[18F]FolyPride作为对细胞外DA水平敏感的DA D2受体的高亲和力PET放射性配体。本研究假设如下：1)D-苯丙胺(0.43 mg/kg P.O.)释放DA将使人纹状体外脑区，如丘脑、边缘区和皮质以及纹状体的[18F]FolyPride的结合电位降低10-15%。2)用α-甲基部分酪氨酸(Ampt，71.4 mg/kg，持续26小时)耗竭DA，将使纹状体外区的[18F]FolyPride结合电位增加约10%-12%，并在男性中引起精神分裂症。这些假说的实现将允许在d-苯丙胺或AMPT之前和之后使用PET[18F]FolyPride研究作为测量人类纹状体外脑区DA释放或基线细胞外DA水平的方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study proposes to develop new methods for measuring d-amphetamine induced dopamine (DA) release and baseline extracellular levels of DA in the thalamus, limbic regions, substantia nigra, and cortex in man. A considerable body of literature indicates that dopaminergic neurotransmission in these regions is centrally involved in the pathophysiology of schizophrenia, psychostimulant drug abuse, and attention deficit disorder. At present there are no methods available for measuring DA release or baseline extracellular DA levels in these regions. We have developed [18F) fallypride as a high affinity PET radioligand for the DA D2 receptor with sensitivity to extracellular DA levels. The hypotheses of this study follows: 1) D-amphetamine (0.43mg/kg p.o.) released DA will produce a 10-15 percent decrease in the binding potentials of [18F] fallypride in extrastriatal brain regions, e.g. thalamus, limbic regions and cortex as well as in striatum in man. 2) DA depletion with alphamethylpartyrosine (AMPT, 71.4 mg/kg over 26 hours) will produce an increase of about 10-12 percent in the [18F] fallypride binding potentials in extrastriatal regions, and schizophrenia in man. The achievement of these hypotheses will allow the use of PET [18F] fallypride studies prior to and following either d-amphetamine or AMPT as methods for measuring DA release or baseline extracellular DA levels in extrastriatal brain regions in man.