The Functional Neuroanatomy of Acute Nicotinic Modulation of Impulsivity in Women

描述（由申请人提供）：本申请用于NIDA I/START（R 03），以检查急性尼古丁纠正女性行为抑制缺陷的发现背后的功能神经解剖学。由于吸烟是美国可预防死亡的主要原因，研究重点是阐明与吸烟易感性、吸烟维持和戒烟失败有关的行为因素。仔细描述这些行为因素的神经生物学基础，有助于吸烟的脆弱性可能会告知吸烟预防和戒烟方法的发展。冲动是一种很有前途的行为内在表型。女性吸烟者比非吸烟者更容易冲动。此外，急性尼古丁已被证明可以降低女性非吸烟者的冲动性。最近的研究已经开始确定涉及测量行为抑制的任务，特别是停止信号任务（SST）的潜在功能神经解剖学。这项拟议的研究将是一项“概念验证”脑成像研究，旨在检查年轻女性吸烟者和非吸烟者SST的潜在功能解剖，并利用fMRI初步评估尼古丁操作对与此任务相关的脑活动的影响。本研究的具体目的是使用功能磁共振成像（fMRI）结合急性药理学挑战（尼古丁与安慰剂），以检查冲动实验室测试期间皮质回路的活动（停止信号任务）在三个仔细表征的受试者组中进行;高冲动女性吸烟者，高冲动女性非吸烟者和低冲动女性非吸烟者。从这项研究中获得的知识将提供一个重要的概念证明。通过功能磁共振成像测量的SST期间的大脑活动对冲动差异敏感。这项研究将有助于我们了解认知/行为过程的神经机制，有助于启动和维持吸烟。这一模式可能对其他滥用药物的检查有用。

DESCRIPTION (provided by applicant): This application is for a NIDA I/START (R03) to examine the functional neuroanatomy underlying the finding that acute nicotine corrects deficits in behavioral inhibition in women. As cigarette smoking is the leading cause of preventable death in the U.S. research has focused on elucidating the behavioral factors that relate to vulnerability to smoking, maintenance of smoking, and failure to quit smoking. Careful characterization of the neurobiological underpinnings of these behavioral factors that contribute to vulnerability to smoking may inform the development of approaches for both smoking prevention and smoking cessation. One promising behavioral endophenotype is impulsivity. Female smokers are known to be more impulsive than non-smokers on several measures of impulsivity. In addition, acute nicotine has been shown to reduce impulsivity in female non-smokers with high impulsivity. Recent studies have begun to identify the underlying functional neuroanatomy involved in tasks that measure behavioral inhibition, particularly the Stop Signal Task (SST). This proposed study will be a "proof of concept" brain imaging study to examine the underlying functional anatomy of the SST in young women smokers and non-smokers and preliminarily evaluate the effects nicotine manipulations on brain activity associated with this task utilizing fMRI. The specific aim of this study is to use functional magnetic resonance imaging (fMRI) combined with acute pharmacologic challenge (nicotine vs placebo) to examine the activity of cortical circuitry during a laboratory test of impulsivity (the Stop Signal Task) in three carefully characterized subject groups; high impulsive female smokers, high impulsive female non-smokers, and low impulsive female non smokers. The knowledge gained from this study will provide an important proof of concept. That the brain activity during the SST as measured by fMRI is sensitive to impulsivity differences. This research will help our understanding of the neural mechanisms of the cognitive/behavioral processes that contribute to the initiation and maintenance, of smoking. This model may be useful for the examination of other drugs of abuse.