PET IMAGING & COCAINE NEUROPHARMACOLOGY IN MONKEYS

这个子项目是许多利用 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来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 开发治疗可卡因成瘾的有效药物将取决于对可卡因神经药理学的更好理解。目前的项目利用正电子发射断层扫描（PET）神经成像技术在非人类灵长类动物作为一种非侵入性的方法来研究可卡因引起的中枢神经系统活动的功能变化。主要的重点是单胺转运体抑制剂对可卡因自我管理和多巴胺神经化学的影响。 我们目前的目标是确定抑制可卡因使用的最佳5-羟色胺转运体占用水平。我们还完成了一系列研究，以确定3，4-亚甲二氧基甲基苯丙胺（MDMA）（一种滥用的苯丙胺类兴奋剂）的神经药理学特征。总体而言，结果支持我们的假设，MDMA的对映体具有不同的药理学选择性多巴胺能和多巴胺能的影响。这可以解释外消旋MDMA在人体内的独特药理学。我们也取得了显着的进展，在清醒的猴子的功能磁共振成像的发展，以表征可卡因和线索诱导的大脑激活在神经回路水平。 我们最近实现了一个眼动跟踪系统，允许在采集血氧水平依赖（BOLD）功能磁共振成像的过程中与显示项目的视觉接触的文档。我们正在使用这个系统来定义当恒河猴暴露于与可卡因自我给药相关的视觉线索时所参与的神经回路。总的来说，这些结果对开发替代激动剂药物治疗兴奋剂滥用具有重要意义。

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. The development of effective medications to treat cocaine addiction will depend on a better understanding of cocaine neuropharmacology. The current project utilized positron emission tomography (PET) neuroimaging techniques in nonhuman primates as a noninvasive approach to investigate cocaine-induced functional changes in central nervous system activity. The major emphasis has been on the effects of monoamine transporter inhibitors on cocaine self-administration and dopamine neurochemistry. Our current goal is to define the optimal level of serotonin transporter occupancy in suppressing cocaine use. We have also completed a long series of studies to characterize the neuropharmacology of 3,4-methylenedioxymethamphetamine (MDMA), an abused amphetamine-type stimulant. Overall, the results support our hypothesis that the enantiomers of MDMA have a distinct pharmacology with selective dopaminergic and serotonergic effects. This may explain the unique pharmacology of racemic MDMA in humans. We have also made significant progress in the development of fMRI in awake monkeys in order to characterize cocaine- and cue-induced brain activation at a neurocircuitry level. We have recently implemented an eye-tracker system that allows for the documentation of visual contact with displayed items during the acquisition of blood oxygenation level dependent (BOLD) fMRI. We are using this system to define the neurocircuitry that is engaged as the rhesus monkeys are exposed to visual cues associated with cocaine self-administration. Collectively, the results have important implication concerning the development of substitute agonist pharmacotherapies to treat stimulant abuse.