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. ? ? ?
