PET IMAGING & COCAINE NEUROPHARMACOLOGY IN MONKEYS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 目前的项目利用正电子发射断层扫描（PET）神经成像和功能性磁共振成像（fMRI）技术在非人类灵长类动物作为一种非侵入性的方法来调查可卡因引起的中枢神经系统活动的功能变化。最近发表的一项研究是第一次使用功能性脑成像来记录非人类灵长类动物在活跃药物使用期间急性可卡因诱导的大脑活动变化。非特遣队管理可卡因后，大脑激活地图归一化为全球流量显示突出的可卡因诱导激活的前额叶皮层主要定位于背外侧区域。然而，由自我施用可卡因引起的大脑激活模式在性质上有所不同。主要激活区域包括前扣带皮层，这是一个与扩展边缘系统相关的区域。当药物相关的刺激的影响，在灭绝过程中确定，有显着增加区域脑血流量在背内侧前额叶皮质，表明强大的皮质激活。结果证明，药物相关刺激可以诱导具有复杂吸毒史的受试者的前额叶皮层的强烈激活。我们也取得了显着的进展，在清醒的恒河猴BOLD功能磁共振成像协议的发展。可卡因诱导的脑激活的特征模式与我们先前使用PET神经成像的研究一致。重要的是，MDMA的影响在性质上是不同的，包括眶额皮质，而可卡因在前扣带回中观察到的影响范围更广。总的来说，这些研究已经确定了有效减少可卡因使用的神经靶点，并表征了与治疗效果相关的潜在神经化学机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The current project utilized positron emission tomography (PET) neuroimaging and functional magnetic resonance imaging (fMRI) techniques in nonhuman primates as a noninvasive approach to investigate cocaine-induced functional changes in central nervous system activity. A recently published study was the first to use functional brain imaging to document acute cocaine-induced changes in brain activity during active drug use in nonhuman primates. Following non-contingent administration of cocaine, brain activation maps normalized to global flow showed prominent cocaine-induced activation of prefrontal cortex localized primarily to the dorsolateral regions. However, the pattern of brain activation induced by self-administered cocaine differed qualitatively. The area of major activation included anterior cingulate cortex, a region associated with the extended limbic system. When the effects of drug-associated stimuli were determined during extinction, there were marked increases in regional cerebral blood flow in the dorsomedial prefrontal cortex, indicating robust cortical activation. The results document that drug-associated stimuli can induce robust activation of prefrontal cortex in subjects with a complex history of drug use. We also have made significant progress in the development of BOLD fMRI protocols in conscious rhesus monkeys. The characteristic pattern of brain activation induced by cocaine was consistent with our previous studies using PET neuroimaging. Importantly, the effects of MDMA were qualitatively different and include the orbitofrontal cortex compared to the more medial extent in the anterior cingulate observed for cocaine. Collectively, these studies have identified neuronal targets to effectively reduce cocaine use and have characterized underling neurochemical mechanisms associated with therapeutic effects.