PET IMAGING & COCAINE NEUROPHARMACOLOGY IN MONKEYS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 治疗可卡因成瘾的有效药物的开发将取决于对可卡因神经药理学的更好理解。目前的项目利用非人类灵长类动物的正电子发射断层扫描(PET)神经成像技术，作为一种非侵入性方法来研究可卡因诱导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给药和多巴胺神经化学的影响。 我们目前的目标是确定5-羟色胺转运体在抑制可卡因使用方面的最佳水平。我们还完成了一系列长时间的研究，以确定3，4-亚甲基二氧基甲基苯丙胺(MDMA)的神经药理学特征，MDMA是一种滥用的苯丙胺类兴奋剂。总体而言，结果支持我们的假设，即MDMA的对映体具有不同的药理作用，具有选择性的多巴胺能和5-羟色胺能作用。这可能解释了外消旋MDMA在人类中的独特药理作用。我们还在清醒猴子的功能磁共振成像方面取得了重大进展，以便在神经回路水平上表征可卡因和线索诱导的大脑激活。 我们最近实施了一个眼睛跟踪系统，该系统允许在采集血氧水平依赖(BOLD)功能磁共振成像期间记录与所显示项目的视觉接触。我们正在使用这个系统来定义恒河猴暴露在与可卡因自我给药相关的视觉线索中时所涉及的神经回路。总之，这些结果对于开发替代激动剂药物疗法来治疗兴奋剂滥用具有重要的意义。

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.