FUNCTIONAL MRI OF HUMAN DRUG ABUSE

可卡因和尼古丁滥用仍然是严重的社会问题， 高累犯率。当人类自我管理时，滥用药物 在局部脑区发挥强大、直接的药理作用 和电路，同时也与特定的认知系统相互作用。的 该项目的总体目标是利用fMRI来定义那些神经元 系统在人类中枢神经系统介导的行动，这两个非常上瘾 药物，并确定可卡因和尼古丁如何与特定的 认知和情感过程。可卡因作用于 人类大脑以及这些回路如何与尼古丁和其他滥用的 代理人知之甚少。此外，几乎没有人知道 它们的神经药代动力学和药效学特性以及神经化学 在人体内的作用部位和机制。本提案的具体目标一 解决了这些药理学问题。然而，人类药物滥用不仅仅是 这是由药物在大脑中的作用来解释的。虽然强大的强化 可卡因的兴奋特性 药物管理在寻求药物和服用药物行为中很重要， 涉及到一系列复杂的、人们知之甚少的行为改变， 一起服用，使吸毒行为永久化。具体目标2解决了 可卡因和尼古丁对认知和情感过程的影响。以来 可卡因成瘾者报告说，他们选择性地回忆起了撞车和展览时的高潮。 很难控制冲动使用和适当称重 使用的风险。因此，假设急性可卡因会增强 持续的注意力和回忆的影响下发生的事件 药物和相应的注意力功能磁共振成像激活的改变 网络（额叶，顶叶，丘脑）和记忆回路（海马） 会被看到。进一步假设急性可卡因会损害 抑制控制、概念形成和注意力转换 特定额叶激活的相应变化。最后我们将 研究急性可卡因给药和情感之间的相互作用 国家测试的假设，即药物的增强性能是 在负面情绪和对可卡因的渴望中增强。更好的 了解这些过程可能会导致更好的行为和/或 可卡因滥用和累犯的药物治疗干预， 确定长期滥用可能导致的认知特征，以帮助 确定最有可能产生依赖性的人。

Cocaine and nicotine abuse remain serious problems in society, with high recidivism rates. When self administered by humans, abused drugs exert powerful, direct pharmacological actions within localized brain regions and circuits, while also interacting with specific cognitive systems. The overall goals of this project are to employ fMRI to define those neuronal systems in the human CNS mediating the actions of these two very addictive agents and to determine how cocaine and nicotine interact with specific cognitive and affective processes. The interplay between where cocaine acts in the human brain and how these circuits overlap with nicotine and other abused agents is poorly understood. Additionally, almost nothing is known regarding their neural pharmacokinetic and pharmacodynamic properties and neurochemical sites and mechanisms of action in humans. Specific Aim I of this proposal addresses these pharmacological issues. However, human drug abuse is not simply explained by where a drug acts in the brain. While the powerful reinforcing and, in the case of cocaine, euphorigenic properties of these drugs are important in drug-seeking and drug-taking behavior, drug administration also engages a complex, poorly understood sequence of behavioral alterations that, taken together, perpetuate drug taking behavior. Specific Aim 2 addresses the effects of cocaine and nicotine on cognitive and affective processes. Since cocaine addicts report selective recall of the high over the crash and exhibit considerable difficulty controlling impulses to use and appropriately weighing risks of use. Therefore, it is hypothesized that acute cocaine will enhance sustained attention and recall for events occurring under the influence of the drug and that corresponding alterations in fMRI activation in attentional networks (frontal, parietal, thalamic) and in memory circuits (hippocampus) will be seen. It is further hypothesized that acute cocaine will impair inhibitory control, concept formation and attention switching with corresponding alterations in specific frontal lobe activation. Finally, we will examine the interaction between acute cocaine administration and affective state to test the hypothesis that the reinforcing properties of the drug are enhanced during times of negative affect and cocaine craving. A better understanding of these processes may lead to better behavioral and/or pharmacological therapeutic interventions for cocaine abuse and recidivism and identify a likely cognitive profile resulting from prolonged abuse to help identify those most at risk for dependence.