HUMAN BRAIN FUNCTION AND DRUG ABUSE

人脑功能与药物滥用

• 批准号: 6431941
• 负责人: ALANE S KIMES
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6431941
• 关键词: brain; brain metabolism; cerebral cortex; clinical research; cocaine; drug addiction; electroencephalography; human subject; magnetic resonance imaging; memory; neural information processing; neuroanatomy; nicotine; positron emission tomography; visual stimulus

This project aims to identify abnormalities in brain function that contribute to dependence on drugs, and to offer leads in developing new treatment modalities. Our strategies include evaluating the relationship between cocaine craving and brain function and between risk taking and brain function in cocaine abusers as measured by positron emission tomography (PET) and [F-18]fluorodeoxyglucose; the relationship between risk taking and brain function and between the ability to inhibit inappropriate responses and brain function using PET and [O-15]water; and determining cognitive effects of nicotine on brain function using the [0-15]-water PET to measure cerebral blood flow. Consistent with findings of a smaller total volume of the prefrontal lobe in substance abusers compared to controls, we found that polydrug abusers (n=30) performed significantly more poorly than controls (n=24) on a risk taking task that is sensitive to orbitofrontal damage in humans, but not on the Wisconsin Card Sorting Task, a standard neuropsychological test of frontal cortical function. Furthermore, in PET studies measuring brain activation during the performance of the risk taking task, drug abusers show less activation in the orbital frontal cortex than control subjects. These data suggest that polydrug abuse is associated with functional deficits in specific portions of the prefrontal cortex. An evaluation of the effects of nicotine on brain function, as measured by PET with [O-15]-water showed that memory performance in 12 abstinent (12 h) nicotine-dependent smokers seems to be mediated by different neural substrates than those in 12 non-dependent controls, suggesting that chronic exposure to nicotine alters cognitive strategies or neural systems subserving memory. Regional activation during performance of a working memory task (N-Back test) was increased by nicotine in controls, but not in smokers, suggesting the development of tolerance.

该项目旨在确定导致药物依赖的大脑功能异常，并为开发新的治疗方式提供线索。 我们的策略包括评估可卡因成瘾者的可卡因渴求与脑功能之间的关系，以及通过正电子发射断层扫描（PET）和[F-18]氟脱氧葡萄糖测量的可卡因滥用者的风险承担与脑功能之间的关系;使用PET和[O-15]水评估风险承担与脑功能之间的关系，以及抑制不适当反应的能力与脑功能之间的关系;以及使用[0-15]-水PET测量脑血流量来确定尼古丁对脑功能的认知效应。 与物质滥用者的前额叶总体积小于对照组的结果一致，我们发现，多药滥用者（n=30）在对人类眶额损伤敏感的冒险任务中的表现显著低于对照组（n=24），但在威斯康星州卡片分类任务中的表现则不佳，这是一种额叶皮质功能的标准神经心理学测试。 此外，在PET研究中，测量在执行冒险任务期间的大脑激活，药物滥用者的眶额皮质比对照组的激活要少。 这些数据表明，多种药物滥用与前额皮质特定部分的功能缺陷有关。 通过PET和[O-15]-水测量尼古丁对脑功能的影响，评价结果显示，12名戒烟（12小时）尼古丁依赖性吸烟者的记忆表现似乎是由与12名非依赖性对照者不同的神经底物介导的，这表明长期暴露于尼古丁会改变认知策略或神经系统，从而影响记忆。 尼古丁在对照组中增加了工作记忆任务（N-Back测试）执行过程中的区域激活，但在吸烟者中没有，这表明耐受性的发展。