FUNCTIONAL MRI OF HUMAN DRUG ABUSE

可卡因和尼古丁滥用仍然是当今社会的严重问题， 尽管有了新的治疗方法，但再次犯罪率仍然很高。虽然它是 普遍认为，强有力的加强和，在这种情况下 可卡因，一种令人愉悦的特性，主要负责 维持寻毒和吸毒行为，人们对此知之甚少 这些药物的神经生物学机制和作用部位。 人类中枢神经系统(CNS)。这样的知识似乎对 最终制定出更成功的治疗策略。AS 因此，这个项目的总体目标是定义这些神经元 人体内调节尼古丁和可卡因作用的系统和回路 CNS并确定这些站点的哪些子集参与其 戒断、渴求和强化属性。作为药理作用 毒剂，可卡因和尼古丁会产生许多深刻的行为和 生理效应。来自动物模型的证据支持他们的观点 与中皮质边缘(MCL)多巴胺系统的相互作用 它们的增强性能。然而，MCL系统的作用既是 而这些药物在人体中的作用地点和作用方式几乎完全未知 由于非侵入性地解决这个问题的工具一直缺乏 必要的敏感性。最后，人们认识到，药物不会对 中枢神经系统内的简单药理作用。他们的强效兴奋剂 属性与环境线索配对，形成条件反射 被认为能够促进持续用药的反应(CRS) 使用和增加复发的可能性。再一次，几乎没有什么是 已知它们的神经解剖基础。据推测， 这些药物激活大脑皮质和皮质下终末区域。 MCLDA系统，这些区域也将被选择性地改变 在慢性药物使用期间，表现为系统功能的改变 在戒毒和渴求期间。与两国之间的关系 大脑的电化学反应，血流和葡萄糖代谢， 神经系统的功能代谢图谱可以使用 人类非侵入性技术的数量。功能磁共振 成像是核磁共振的一种非常新的应用，它允许检查 不使用X射线或电离的功能性脑活动 辐射。其出色的时间(秒)和空间(2-3毫米) 分辨率允许在主题设计内进行虚拟的实时成像 其他目前的程序是不可能的。这项建议将利用 这项新技术可以确定大脑的神经解剖学作用部位 尼古丁和可卡因以及这些药物改变神经元的能力 执行被认为激活的认知任务时的响应性 神经元DA终末区域。我们还将研究时间进程 退缩与线索诱发的渴求对“休息”和“休息”的影响 任务诱导的神经元激活。我们还将解决以下问题 人脑中的强化回路。希望这些数据 可能最终导致更好地理解，并制定战略 治疗毒瘾，反过来又减少了再犯罪率。

Cocaine and nicotine abuse remain serious problems in today's society, and despite new treatments, recidivism rates remain high. While it is generally agreed that the powerful reinforcing and, in the case of cocaine, euphorigenic properties, are principally responsible for maintaining drug-seeking and drug-taking behavior, little is known about the neurobiological mechanisms and sites of action of these agents in the human central nervous system (CNS). Such knowledge appears necessary for the ultimate development of more successful treatment strategies. As such, the overall goal of this project is to define those neuronal systems and circuits mediating nicotine and cocaine actions in the human CNS and to determine which subset of these sites participate in their withdrawal, craving and reinforcing properties. As pharmacological agents, cocaine and nicotine produce a number of profound behavioral and physiological effects. Evidence from animal models support their interaction with the mesocorticolimbic (MCL) dopamine system in producing their reinforcing properties. However, both the role of the MCL system and where and how these drugs act in humans is almost completely unknown as the tools to noninvasively address this question have lacked the necessary sensitivity. Finally, it is recognized that drugs do not exert a simple pharmacological action within CNS. Their powerful stimulant properties become paired with environmental cues to form conditioned responses (CRs) which are thought to be able to promote continued drug use and increase relapse probability. Once again, virtually nothing is known regarding their neuroanatomic substrates. It is hypothesized that these agents activate cortical and subcortical terminal fields of the MCLDA system and that these regions will also be selectively altered during chronic drug use as manifest by alterations in system functioning during drug withdrawal and craving. With the relationship between cerebral electrochemical activity, blood flow and glucose metabolism, functional metabolic mapping of the nervous system is possible using a number of noninvasive techniques in man. Functional magnetic resonance imaging is a very new application of MRI that permits an examination of functional cerebral activity without the use of X-rays or ionizing radiation. Its excellent temporal (seconds) and spatial (2-3 mm) resolution permits virtual 'real time' imaging and within subject designs not possible with other current procedures. This proposal will utilize this novel technique to determine the neuroanatomic sites of action of nicotine and cocaine and the ability of these drugs to alter neuronal responsivity when performing cognitive tasks believed to activate neuronal DA terminal regions. We will also examine the time course of withdrawal and the effects of cue-induced craving on both "resting" and task-induced neuronal activation. We will also address the question of reinforcement circuitry in the human brain. It is hoped that these data may eventually lead to better understanding of, and strategies for treating drug addiction, producing, in turn, a decrease in recidivism.