Are Some Regular Smokers Resistant to Nicotine Dependence?

描述（由申请方提供）：目前尼古丁成瘾的理论模型假设尼古丁使用的强度和持续时间与尼古丁依赖的发展之间存在相对密切的关系。然而，这种关系比人们预期的要弱;使用度量通常只占依赖性方差的一小部分。此外，许多长期、重度每日吸烟者未能满足DSM- IV依赖性标准。使用和依赖性之间的弱关系可能是由于依赖性测量不充分或不敏感、尼古丁暴露的充分表征和/或某些重度吸烟者对尼古丁依赖的相对抵抗力。本申请的目的是利用已建立的人类实验室程序来严格评估吸烟者亚群尽管广泛使用尼古丁但可能相对抵抗尼古丁依赖的可能性。具体目标是：1）确定不符合DSM-IV尼古丁依赖标准的个体是否也根据其他自我报告措施表现出较低的依赖性; 2）确定吸烟行为流行病学措施中未评估的使用/暴露特征是否可以解释尼古丁依赖的个体差异; 3）确定自我报告的依赖性指标的差异是否可以预测在具有相似尼古丁使用史的个体中，当给予激励时，谁能够避免吸烟。在拟定的研究中，我们将招募沿着当前使用（5-10支vs 20支以上/天）和DSM-IV依赖（依赖vs非依赖）标准变化的个体，采用2 x 2设计。我们预测，不符合DSM-IV尼古丁依赖标准的个体将通过其他连续的多维测量来评估相对较低的依赖水平，并且这些差异将无法通过尼古丁使用/暴露来完全解释。此外，我们预计个人未能满足DSM-IV的依赖，更有能力避免吸烟的禁欲测试比DSM-IV依赖的吸烟者。这些研究结果表明，具有可比尼古丁使用的吸烟者中出现的DSM-IV依赖性的个体差异代表了发展尼古丁依赖的脆弱性的真实的差异，值得进一步研究。这项拟议中的研究将确定一些经常长期吸烟的人是否对尼古丁依赖有相对的抵抗力。如果确定了这样一个亚群，未来的研究将解决尼古丁依赖发展所必需的因素，或者相反，什么因素可能保护一些人免于高度依赖。确定尼古丁依赖个体差异的机制可能会突出预防和治疗尼古丁成瘾的新方法。

DESCRIPTION (provided by applicant): Current theoretical models of nicotine addiction assume a relatively close relationship between the intensity and duration of nicotine use and the development of nicotine dependence. However, this relationship is weaker than one might expect; use measures typically account for only a small portion of the variance in dependence. Furthermore, many long-time, heavy daily smokers fail to meet DSM- IV dependence criteria. The weak relationship between use and dependence may result from inadequate or insensitive measures of dependence, adequately characterizations of nicotine exposure, and/or relative resistance to becoming nicotine dependent in some heavy cigarette users. The purpose of this application is to utilize established human laboratory procedures to rigorously assess the possibility that a subpopulation of smokers may be relatively resistant to becoming nicotine dependent despite extensive nicotine use. The specific aims are: 1) To determine whether individuals who fail to meet DSM-IV criteria for nicotine dependence also exhibit lower dependence according to other self-report measures; 2) To determine whether use/exposure characteristics not assessed in epidemiological measures of smoking behavior can account for individual differences in nicotine dependence; 3) To determine whether differences in self-report measures of dependence predict who will be able to refrain from smoking when given an incentive to do so among individuals with similar nicotine use histories. In the proposed study, we will recruit individuals who vary along both current use (5-10 versus 20+ cigarettes/day) and DSM-IV dependence (dependent versus non- dependent) criteria in a 2 x 2 design. We predict that individuals failing to meet criteria for DSM-IV nicotine dependence will demonstrate relative low levels of dependence is assessed by other continuous, multidimensional measures, and that these differences will not be fully explained by nicotine use/exposure. Furthermore, we expect individuals failing to meet DSM-IV dependence to be more capable of refraining from cigarette use in an abstinence test than DSM-IV dependent smokers. These findings would suggest that individual differences in DSM-IV dependence that arise in smokers with comparable nicotine use represent real differences in vulnerability to developing nicotine dependence that deserve further research. The proposed study will determine whether some regular, prolonged smokers are relatively resistant to becoming nicotine dependent. If such a subpopulation is identified, future studies will address what factors may be necessary for nicotine dependence to develop or, conversely, what factors might protect some individuals from becoming highly dependent. Identifying the mechanisms which account for individual differences in nicotine dependence may highlight novel approaches to both prevention and treatment of nicotine addiction.