FUNCTIONAL BRAIN MAPPING OF COCAINE ACTION

可卡因作用的大脑功能图谱

• 批准号: 6515535
• 负责人: BRUCE R ROSEN
• 金额: $ 109.08万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6515535
• 关键词: bioimaging /biomedical imaging; brain imaging /visualization /scanning; brain mapping; cocaine; drug addiction; functional magnetic resonance imaging

A major unmet goal of drug abuse research is to understand the neural substrates of reinforcement of drugs of abuse in humans and the role that these mechanisms may play in initiating and sustaining drug dependence. This proposal for a Program Project is a renewal of our currently funded PO1 from the National Institute on Drug Abuse, "fMRI of Cocaine Action". The overall goal of this program continues to be the utilization and refinement of state of the art techniques to produce interpretable brain maps, functional anatomy of human subjective states that occur in response to c0caine, with particular emphasis during the funding cycle on the braid reward circuitry mediating cocaine response in humans, using functional magnetic resonance imaging (fMRI) as the principal tool. To effectively perform the experiments to test these hypotheses, three Projects and three Cores. As in our current funding cycle, Project 1 is an fMRI study of regional brain activation by cocaine in cocaine-dependent human subjects. The objective of Project 1 is to investigate of brain reward circuitry in mediating the cocaine response in humans, and to distinguish euphoria-like brain activation from craving-like brain activation. Project 2 has evolved to begin the important work of developing rodent models to more completely understand pharmacologically mediated MRI signal changes observed after administration of dopamine ligands. The studies proposed in Project 2 are of fundamental importance for understanding and interpreting functional imaging data following cocaine administration in animals and humans. Project 3 utilizes rodent models, including both drug-naive and cocaine- dependent rats and, new to this funding cycle, knockout mice, to address specific pharmacological and drug dependence issues which cannot be readily addressed in humans. We anticipate that results from these experiments, will identify the role of particular neurotransmitter mechanisms (namely, dopaminergic and serotonergic) that underlie the pattern of cocaine-induced brain activation. The hypothesis driven experiments using state of the art functional imaging techniques that we proposed in Project 1, in concert with experiments proposed in Project 2 focused on identifying mechanisms coupling psychostimulant administration to cerebrovascular response, are designed to provide a deeper understanding of the mechanism of cocaine action. The Program Project mechanism is ideal for a multi-disciplinary project with these goals in mind. We anticipate that the experiments in rodents will advance our understanding of acute and chronic effects of cocaine on brain function, facilitating interpretation of data from Project 1, thereby providing a crucial effects of cocaine on brain function, facilitating interpretation of data from Project, thereby providing a crucial link in understanding the fMRI correlates and neurobiology consequences of cocaine addiction in humans.

药物滥用研究的一个主要未实现的目标是了解人类滥用药物强化的神经基质以及这些机制在引发和维持药物依赖中可能发挥的作用。这项计划项目提案是对我们目前由国家药物滥用研究所资助的 PO1“可卡因作用的功能磁共振成像”的更新。该计划的总体目标仍然是利用和完善最先进的技术来生成可解释的大脑图谱，对可卡因反应中发生的人类主观状态的功能解剖学，特别是在资助周期内以功能磁共振成像（fMRI）为主要工具，重点研究介导人类可卡因反应的编织奖励电路。为了有效地进行实验来检验这些假设，需要三个项目和三个核心。与我们当前的资助周期一样，项目 1 是一项功能磁共振成像研究，研究可卡因依赖的人类受试者中可卡因的区域大脑激活情况。项目 1 的目标是研究调节人类可卡因反应的大脑奖赏回路，并区分欣快型大脑激活和渴望型大脑激活。项目 2 已开始开展开发啮齿动物模型的重要工作，以更全面地了解给予多巴胺配体后观察到的药理学介导的 MRI 信号变化。项目 2 中提出的研究对于理解和解释动物和人类服用可卡因后的功能成像数据至关重要。项目3利用啮齿动物模型，包括未接触药物和可卡因依赖的大鼠，以及本资助周期中的新基因敲除小鼠，来解决人类无法轻易解决的特定药理学和药物依赖问题。我们预计这些实验的结果将确定可卡因诱导的大脑激活模式背后的特定神经递质机制（即多巴胺能和血清素能）的作用。我们在项目 1 中提出的假设驱动实验使用最先进的功能成像技术，与项目 2 中提出的实验相结合，重点是确定精神兴奋剂给药与脑血管反应的耦合机制，旨在提供对可卡因作用机制的更深入的理解。计划项目机制对于考虑到这些目标的多学科项目来说是理想的。我们预计，在啮齿动物身上进行的实验将增进我们对可卡因对大脑功能的急性和慢性影响的理解，促进对项目1数据的解释，从而提供可卡因对大脑功能的关键影响，促进对项目数据的解释，从而为理解人类可卡因成瘾的功能磁共振成像相关性和神经生物学后果提供重要的联系。