FMRI STUDY OF CNS PHYSIOLOGY DURING COCAINE RESPONSE

描述(申请人摘要)： 这项名为《可卡因生理偶联的fMRI研究》的提案 回应“，是为了回应NIDA计划对 导师研究科学家发展奖(K01)。候选人寻求 接受药物滥用的神经生物学方面的培训，同时做出贡献 加强我们对可卡因引起的大脑变化的理解的研究 生理和功能磁共振信号在这些变化方面的解释。 凭借其高空间和时间分辨率的独特组合， 通过磁共振成像(FMRI)进行功能脑电地形图有很大的优势 可能有助于我们理解药物的神经生物学 上瘾。急性药物研究中早期的fMRI经验表明 只有fMRI血氧水平依赖(BOLD)的T2*变体 信号和CBV加权信号-具有功能灵敏度，可检测 个体药物刺激引起的小脑区局灶性激活 研究对象。大胆信号和CBV的不确定性解释 血流灌注是预测新陈代谢的最好的血流动力学指标。 这是个重大问题。这项提议涉及多步骤联系的一部分 神经元活动与功能磁共振信号--功能磁共振之间的关系 信号和潜在的代谢和血流动力学改变 可卡因的使用。拟议研究的目标是 分别测量基本的功能磁共振可观测组-CBF、CBV、BOLD信号、 和CMR02-在大鼠模型中对可卡因的功能反应期间，以及 确定每个量与葡萄糖新陈代谢的关系。 基本假设是脑血流动力学和代谢 对精神活性药物的改变以可识别的方式结合在一起，并且 粗体信号的测量-这些变量的复杂组合 是目前人类选择的功能磁共振成像工具-可以可靠地与 血流灌注和葡萄糖代谢的变化。将进行测量 在两种大鼠模型中：1)氟烷麻醉的幼鼠； 急性可卡因后哪个区域的葡萄糖代谢增加 在清醒、幼稚的大鼠中，给药与类似的测量结果相关 2)长期暴露于可卡因的大鼠，这是一种有望表现出 改变了生理学。这些研究试图验证生理学基础 为研究大脑中精神活性药物的作用提供了一种很有前途的新技术 并增加我们对可卡因的神经生物学的了解。

DESCRIPTION (Applicant's Abstract): This proposal, "fMRI Study of Physiological Couplings During Cocaine Response", is submitted in response to the NIDA program anouncement for Mentored Research Scientist Development Awards (K01). The Candidate seeks to gain training in the neurobiology of drug abuse while contributing research that enhances our understanding of cocaine-induced changes in brain physiology and the interpretation of fMRI signal in terms of those changes. With its unique combination of high spatial and temporal resolution, functional brainmapping by magnetic resonance imaging (fMRI) has great potential to contribute to our understanding of the neurobiology of drug addiction. The early fMRI experience in acute drug studies suggests that only the T2* variants of fMRI blood oxygenation level dependent (BOLD) signal and CBV-weighted signal - have the functional sensitivity to detect focal activation in small brain regions due to drug stimuli in individual subjects. The uncertain interpretation of BOLD signal and CBV in terms of perfusion, the best hemodynamic predictor of metabolism, remains a significant issue. This proposal addresses one part of the multi-step link between neuronal activity and fMRI signal - the relationship between fMRI signal and underlying metabolic and hemodynamic alterations due to administration of cocaine. The goal of the proposed research is to separately measure the base set of fMRI observables - CBF, CBV, BOLD signal, and CMR02 - during a functional response to cocaine in a rat model, and to determine the relationships that couple each quantity to glucose metabolism. The fundamental hypothesis is that cerebral hemodynamic and metabolic alterations to a psychoactive drug are coupled in identifiable ways, and measurements of BOLD signal - a complex combination of these variables which is currently the fMRI tool of choice in humans- can be reliably related to changes in perfusion and glucose metabolism. Measurements will be performed in two rat models: 1) naive rats anesthetized by halothane, a model in which regional increases in glucose metabolism following acute cocaine administration correlate with similar measurements in awake, naive rats, and 2) rats chronically exposed to cocaine, a model which is expected to exhibit altered physiology. These studies seek to validate the physiological basis of a promising new technology for study of psychoactive drug action in brain and to increase our understanding of the neurobiology of cocaine.