Nicotine Receptor Density & Dopamine System Function

描述（由申请人提供）：吸烟是全球死亡和残疾的主要原因。大多数烟草依赖的吸烟者赞同戒烟的愿望，但很少（约2%至5%）能够自己戒烟，即使经过综合治疗（包括药物和心理治疗），也只有不到一半的吸烟者能够成功戒烟。更好地了解当前一线治疗对大脑尼古丁恢复和奖励系统功能的影响可能会改善吸烟治疗。 先前的研究表明，长期接触香烟或尼古丁会导致大脑中尼古丁受体数量的增加。我们小组的初步数据还表明，每天吸烟的人大脑中对吸烟做出反应的化学物质多巴胺的释放减少了。本文提出的研究目的是确定吸烟（和/或戒烟）治疗是否会导致大脑中尼古丁受体数量和吸烟诱导的多巴胺释放正常化。 对于拟议的研究，我们将确定实用团体咨询（PGC）（心理治疗）和盐酸安非他酮（Zyban）治疗对尼古丁受体密度和吸烟诱导的多巴胺释放的影响。一般的程序是，吸烟者将接受两种类型的正电子发射断层扫描（PET）扫描，以检查这两个方面的脑功能之前和之后的12周疗程的PGC，盐酸安非他酮，或药丸安慰剂（受试者将被随机分配到治疗）。非吸烟者和既往吸烟者也将接受PET扫描作为对照组。该设计将允许确定尼古丁受体可用性和吸烟诱导的多巴胺释放从吸烟积极治疗前后的变化，并确定治疗中观察到的变化是否代表功能正常化。 我们假设，吸烟者接受积极治疗（心理治疗或盐酸安非他酮）将有更大的尼古丁受体和多巴胺释放的正常化比吸烟者接受安慰剂治疗。我们还假设，戒烟的吸烟者比不戒烟者的这些功能更正常。此外，我们将检查与戒烟相关的症状（如渴望，焦虑和抑郁），我们的理论是，这些症状在尼古丁受体密度和多巴胺释放异常更严重的吸烟者中会更严重。最后，我们将检查基线时大脑异常的程度是否可以预测谁会对减少或戒烟的治疗有反应，基线时异常程度较轻的吸烟者比异常程度更严重的吸烟者更容易戒烟。

DESCRIPTION (provided by applicant): 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.