FUNCTIONAL BRAIN MAPPING OF COCAINE ACTION

药物滥用研究尚未实现的一个主要目标是了解人类滥用药物强化的神经基础以及这些机制在引发和维持药物依赖性方面可能发挥的作用。这个计划项目的建议是我们目前资助的PO1从国家药物滥用研究所的更新，“功能性磁共振成像的药物滥用行动”。该计划的总体目标仍然是利用和完善最先进的技术，以产生可解释的大脑地图，对可卡因产生反应的人类主观状态的功能解剖学，特别强调在资助周期期间，使用功能性磁共振成像（fMRI）作为主要工具，介导人类可卡因反应的辫子奖励电路。为了有效地进行实验来验证这些假设，三个项目和三个核心。在我们目前的资助周期中，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的可卡因局部大脑激活。项目1的目的是研究大脑奖赏回路在介导人类可卡因反应中的作用，并区分欣快样大脑激活和渴望样大脑激活。项目2已经发展到开始开发啮齿动物模型的重要工作，以更全面地了解多巴胺配体给药后观察到的多巴胺介导的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可卡因给药后的功能成像数据具有根本重要性。项目3利用啮齿类动物模型，包括未使用过药物的大鼠和可卡因依赖的大鼠，以及本供资周期的新的基因敲除小鼠，以解决在人类中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，将确定特定的神经递质机制（即多巴胺能和多巴胺能）的作用，可卡因诱导的大脑激活模式的基础。我们在项目1中提出的使用最先进的功能成像技术的假设驱动实验，与项目2中提出的实验一致，重点是确定将精神兴奋剂给药与脑血管反应耦合的机制，旨在更深入地了解可卡因的作用机制。计划项目机制是理想的多学科项目与这些目标铭记。我们预计，啮齿类动物的实验将促进我们对可卡因对脑功能的急性和慢性影响的理解，促进项目1数据的解释，从而提供可卡因对脑功能的关键影响，促进项目数据的解释，从而为理解人类可卡因成瘾的fMRI相关性和神经生物学后果提供关键联系。

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.