Effect of Exposure to Nicotine Vapor on the Vulnerability to Nicotine Dependence

描述(由申请人提供)：烟草使用在美国仍然是一个主要的公共健康问题，三分之一的吸烟者变得依赖，吸烟是美国主要的可避免的死亡原因。仅在美国，非吸烟者接触烟草烟雾(二手烟暴露)被认为导致额外5万人死于心脏病和癌症，100万人肺部和耳朵感染，另外100万儿童哮喘发作增加。电子烟使用的快速增长可能会对人口产生戏剧性的后果。电子烟行业去年在美国创造了超过10亿美元的收入，预计到2047年将超过传统香烟的销售。此外，电子烟的危险在于，它们在市场上被宣传为可以安全使用，但几乎没有人对尼古丁蒸气暴露对大脑的影响和尼古丁依赖的发展进行过研究。二手烟和电子烟的使用会导致临床上显著的血液尼古丁水平。我们假设，它们将产生重要的神经适应，从而增加发展成瘾和促进复发的风险。目前的建议侧重于动物研究，以调查吸入尼古丁在 水平与电子烟相似，对尼古丁依赖和复发的发展。第一种假设是，长期接触浓度与电子烟相似、甚至更低的尼古丁蒸气，会影响与尼古丁依赖相关的关键行为(焦虑样行为、痛觉过敏)。第二种假设是，长期接触浓度与电子烟相似、甚至更低的尼古丁蒸气，会增加尼古丁摄入量的升级，并在戒烟一段时间后引发复发。为了确定尼古丁吸入的确切效果，我们开发了一种创新的吸入系统，将大鼠暴露在空气中已知浓度的尼古丁中。这种新的尼古丁吸入动物模型的使用将提供一个独特的机会来确定尼古丁暴露的最低水平，这是产生可能促进尼古丁依赖获得和复发的行为变化所必需的。这些研究的结果将提供(1)增加尼古丁依赖风险所需的最低剂量的尼古丁蒸气；(2)电子烟的使用是否与获得尼古丁依赖和重新依赖尼古丁的风险增加有关的证据；(3)为尼古丁依赖预防工作和政策制定者提供重要信息。

DESCRIPTION (provided by applicant): Tobacco use continues to be a major public health problem in the United States, with one-third of users becoming dependent, and tobacco smoking is the leading avoidable cause of death in the United States. In the United States alone, exposure to tobacco smoke by nonsmokers (second-hand smoke exposure) is believed to cause an additional 50,000 deaths from heart disease and cancer, 1 million lung and ear infections, and increased asthma episodes in an additional 1 million children. The rapid growth of electronic cigarette use may have dramatic consequences on the population. The electronic cigarette industry generated over $1 billion in revenue in the United States last year and is predicted to pass traditional cigarette sales by 2047. Moreover, the danger of electronic cigarette is that they are marketed as safe to use, but virtually no research has been conducted on the consequences of nicotine vapor exposure on the brain and development of nicotine dependence. Second-hand smoke and electronic cigarette use lead to clinically significant blood nicotine levels. We hypothesize that they will produce important neuroadaptations that contribute to increased risk of developing dependence and facilitating relapse. The present proposal focuses on animal studies to investigate the specific effects of inhalation of nicotine at levels similar to electronic cigarettes on the development of nicotine dependence and relapse. The first hypothesis is that chronic exposure to nicotine vapor at concentrations similar to electronic cigarettes, or even lower, will affect key behaviors related to nicotine dependence (anxiety-like behavior, hyperalgesia). The second hypothesis is that chronic exposure to nicotine vapor at concentrations similar to electronic cigarettes, or even lower, will increase the escalation of nicotine intake and provoke relapse after a period of abstinence. To determine the exact effect of nicotine inhalation, we developed an innovative inhalation system to expose rats to known concentrations of nicotine in the air. The use of this new animal model of nicotine inhalation will provide a unique opportunity to determine the lowest level of nicotine exposure that is required to produce behavioral changes that may facilitate the acquisition of and relapse to nicotine dependence. The results of these studies will provide (i) the lowest dose of nicotine vapor required to increase the risk for nicotine dependence, (ii) evidence of whether electronic cigarette use is associated with increased risk of the acquisition of and relapse to nicotine dependence, and (iii) important information for nicotine dependence prevention efforts and policymakers.