PET IMAGING OF EXTRASTRIATAL DOPAMINE LEVELS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 本研究提出了一种新的方法来测量d-苯丙胺诱导的多巴胺（DA）释放和基线细胞外水平的DA在丘脑，边缘系统区域，黑质，和cortex在man.A相当大的身体的文献表明，多巴胺能神经传递在这些地区集中参与精神分裂症，精神兴奋剂药物滥用，注意力缺陷障碍的病理生理。 目前，没有方法可用于测量这些区域中的DA释放或基线细胞外DA水平。 我们已经开发了[18F] fallypride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。 本研究的假设如下： 第一章 D-苯丙胺（0.43 mg/kg p.o.） 释放的DA将使[18 F] fallypride在纹状体外脑区（例如丘脑、边缘区和皮质）以及人的纹状体中的结合电位降低10- 15%。 （二） 用N-甲基酪氨酸（AMPT，71.4 mg/kg，26小时）消耗DA将使纹状体外区域的[18 F] fallypride结合潜力增加约10- 12%，并使人精神分裂症。 这些假设的实现将允许使用PET [18 F] fallypride研究之前和之后的d-苯丙胺或AMPT作为测量DA释放或基线细胞外DA水平的方法在人的纹状体外脑区。

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.