Cigarette smoking is a major cause of death and disability worldwide. Most tobacco dependent smokers endorse a desire to quit, but very few (about 2 to 5%) are able to do so on their own and less than half of smokers who try quitting will be successful even with comprehensive treatment (including medication and psychotherapy). A greater understanding of the effects of current first-line treatments on recovery of brain nicotine and reward system functioning may lead to improved treatments for cigarette smoking. Prior research demonstrates that chronic exposure to cigarettes or nicotine results in an increased number of nicotine receptors in the brain. Pilot data from our group also suggests that release of the chemical dopamine in the brain in response to smoking is decreased in daily smokers. The objective of the research proposed here is to determine if treatment for smoking (and/or quitting smoking) results in a normalization of the number of nicotine receptors in the brain and of smoking-induced release of dopamine. For the proposed studies, we will determine the effects of treatment with practical group counseling (PGC) (psychotherapy) and bupropion HCl (Zyban) on the density of nicotine receptors and on smoking-induced dopamine release. The general procedure is that cigarette smokers will undergo two types of positron emission tomography (PET) scanning to examine these two aspects of brain function both before and after a 12-week course of treatment with either PGC, bupropion HCl, or pill placebo (subjects will be randomly assigned to the treatments). Non-smokers and former smokers will also be scanned with PET as control groups. This design will allow for the determination of changes in nicotine receptor availability and in smoking-induced dopamine release from before to after active treatments for cigarette smoking, and to determine if the changes seen with treatment represent a normalization of function. We hypothesize that smokers treated with active treatments (psychotherapy or bupropion HCl) will have greater normalization of nicotine receptors and dopamine release than smokers treated with placebo. We also hypothesize that smokers who quit smoking will have greater normalization of these functions than non-quitters. In addition, we will examine symptoms associated with withdrawal from cigarettes (such as craving, anxiety, and depression), and we theorize that these symptoms will be worse in smokers with more severe abnormalities in nicotine receptor density and dopamine release. Finally, we will examine whether or not the degree of brain abnormality at baseline predicts who will respond to treatment in terms of reducing or quitting smoking, with smokers with less severe abnormalities at baseline having an easier time quitting than smokers with more severe abnormalities.
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