This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cigarette smoking is the leading cause of preventable death in the U.S. and female smokers have more difficulty quitting smoking than do male smokers. Understanding the factors that relate to vulnerability to smoking, maintenance of smoking, and failure to quit smoking is an important goal of behavioral research. Careful characterization of the neurobiological underpinnings of behavioral factors that contribute to vulnerability to smoking may help to develop more effective interventions for both smoking prevention and smoking cessation. One promising behavioral characteristic related to cigarette smoking in women is impulsivity. Female smokers are known to be more impulsive than non-smokers on several different measures of impulsivity. In addition, acute nicotine has been shown to reduce impulsivity in female non-smokers who are highly impulsive. Recent studies have begun to identify the underlying functional neuroanatomy involved in tasks that measure impulsivity particularly the Stop Signal Task (SST). The goal of this research study is to examine changes in brain activity associated with improvements in impulsivity related to nicotine administration in women. This is a pilot brain imaging study examining patterns of brain activation during performance of the Stop Signal Task (a test of impulsivity) in women smokers and non-smokers. Three groups of women will be studied;high impulsive female smokers, high impulsive female non-smokers, and low impulsive female non-smokers. Each subject will participate in two study days during which they will have their impulsivity assessed while in the MRI scanner. On one day subjects will take nicotine and on one day they will take placebo. Medication will be administered in a double blind fashion and the order of drug and placebo will be randomized. The knowledge gained from this study will provide an important """"""""proof of concept"""""""" that the brain activity during the Stop Signal Task as measured by fMRI is sensitive to differences in impulsivity which is modifiable by nicotine. This research will help our understanding of the neural mechanisms of one of the behavioral processes that contribute to the initiation and maintenance of smoking. This model may additionally be useful for the examination of other drugs of abuse.
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