FUNCTIONAL MRI OF HUMAN DRUG ABUSE

可卡因和尼古丁滥用仍然是社会上的严重问题， 高累犯率。当人类自行给药时，滥用药物 在局部脑区发挥强大、直接的药理作用 和回路，同时也与特定的认知系统相互作用。这个 这个项目的总体目标是使用功能磁共振成像来定义这些神经元 人类中枢神经系统中调节这两种非常令人上瘾的行为的系统 并确定可卡因和尼古丁如何与特定的 认知和情感过程。可卡因的作用区域之间的相互作用 人类大脑以及这些回路如何与尼古丁和其他滥用的 特工们对此知之甚少。此外，人们对此几乎一无所知 它们的神经药代动力学和药效学特性及神经化学 人体内的作用部位和机制。这项建议的具体目标一 解决这些药理学问题。然而，人类吸毒并不是简单的 通过药物在大脑中的作用来解释。而强大的补强 而且，在可卡因的情况下，这些药物的愉悦特性是 在寻找毒品和吸毒行为中很重要，药物管理也 参与了一系列复杂的、鲜为人知的行为改变， 综上所述，这将使吸毒行为永久化。特定目标2解决了 可卡因和尼古丁对认知和情感过程的影响。自.以来 可卡因成瘾者报告说，在撞车和展品上选择性地回忆起了兴奋 很难控制冲动的使用和适当的权衡 使用风险。因此，假设急性可卡因会增强 持续关注和回忆在以下因素影响下发生的事件 药物及其在注意障碍中功能磁共振激活相应改变 网络(额叶、顶叶、丘脑)和记忆回路(海马体) 将会见分晓。进一步的假设是急性可卡因会损害 抑制控制、概念形成和注意转换 额叶特异性激活的相应变化。最后，我们会 研究急性可卡因给药与情感性精神障碍之间的相互作用 以检验药物的增强特性是 在消极情绪和对可卡因的渴求时期得到加强。更好的 了解这些过程可能会导致更好的行为和/或 对可卡因滥用和复发的药物治疗干预和 找出长期虐待可能导致的认知特征，以帮助 找出那些依赖风险最大的人。

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.