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

烟草使用仍然是美国的一个主要公共卫生问题，三分之一的使用者成为依赖者，吸烟是美国可避免的主要死因。仅在美国，非吸烟者暴露于烟草烟雾（二手烟暴露）据信会导致另外50，000人死于心脏病和癌症，100万人肺部和耳部感染，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巨大影响。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年将超过传统卷烟的销售额。此外，电子烟的危险在于它们被销售为使用安全，但实际上没有研究尼古丁蒸汽暴露对大脑的影响和尼古丁依赖的发展。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，有助于增加发展依赖和促进复发的风险。目前的建议侧重于动物研究，以调查吸入尼古丁的具体影响， 水平类似于电子香烟对尼古丁依赖和复发的发展。第一个假设是，长期暴露于浓度与电子烟相似甚至更低的尼古丁蒸汽，将影响与尼古丁依赖相关的关键行为（焦虑样行为，痛觉过敏）。第二个假设是，长期暴露于浓度与电子烟相似甚至更低的尼古丁蒸汽，将增加尼古丁摄入量的增加，并在戒烟一段时间后引起复发。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，使大鼠暴露于空气中已知浓度的尼古丁。使用这种新的尼古丁吸入动物模型将提供一个独特的机会，以确定产生可能促进尼古丁依赖获得和复发的行为变化所需的最低尼古丁暴露水平。这些研究的结果将提供（i）增加尼古丁依赖风险所需的最低尼古丁蒸汽剂量，（ii）电子烟使用是否与尼古丁依赖获得和复发风险增加相关的证据，以及（iii）尼古丁依赖预防工作和政策制定者的重要信息。

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.