PET IMAGING & COCAINE NEUROPHARMACOLOGY IN MONKEYS

宠物成像

• 批准号: 8357377
• 负责人: LEONARD L HOWELL
• 金额: $ 4.12万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357377
• 关键词: Acute; Anterior; Area; Brain; Brain imaging; Cerebrovascular Circulation; Characteristics; Cocaine; Complex; Conscious; Development; Drug usage; Extinction (Psychology); Functional Magnetic Resonance Imaging; Funding; Grant; Image; Imaging Techniques; Limbic System; Macaca mulatta; Maps; Medial; Monkeys; National Center for Research Resources; Neuraxis; Neurons; Neuropharmacology; Pattern; Pharmaceutical Preparations; Positron-Emission Tomography; Prefrontal Cortex; Primates; Principal Investigator; Protocols documentation; Publishing; Recording of previous events; Research; Research Infrastructure; Resources; Self-Administered; Source; Stimulus; Therapeutic Effect; United States National Institutes of Health; cingulate cortex; cocaine use; cost; ecstasy; neurochemistry; neuroimaging; nonhuman primate

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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 当前的项目利用非人类灵长类动物中的正电子发射断层扫描（PET）神经影像学和功能性磁共振成像（fMRI）技术作为一种无创方法，用于研究中枢神经系统活动中可卡因诱导的功能变化。最近发表的一项研究是第一个使用功能性脑成像记录急性可卡因诱导的非人类灵长类动物使用药物使用期间的脑活动变化的研究。在非固定施用可卡因后，脑部激活图归一化为全球流动，显示可卡因诱导的明显的前额叶皮层激活主要位于背外侧区域。但是，自我管理可卡因引起的大脑激活模式在定性上有所不同。主要激活区域包括前扣带回皮层，这是与扩展边缘系统相关的区域。当在灭绝期间确定与药物相关的刺激的作用时，背侧额叶前额叶皮层的区域脑血流量明显增加，表明皮质稳定的皮质激活。结果表明，与药物相关的刺激可以诱导具有复杂使用药物使用史的受试者的前额叶皮层的强化激活。我们还在有意识的恒河猴中大胆的fMRI方案的发展方面取得了重大进展。可卡因引起的脑激活的特征模式与我们先前使用PET神经影像学的研究一致。重要的是，在可卡因观察到的前扣带回中，MDMA的作用在质量上不同，包括眶额皮质。总的来说，这些研究已经确定了神经元靶标，以有效地减少可卡因的使用，并表征了与治疗作用相关的神经化学机制。