Flavored e-cigarette use in adolescents: Behavioral, cellular, and epigenetic mechanisms

电子烟越来越多地被青少年使用，他们特别容易上瘾 尼古丁的特性由于不含薄荷醇，因此已禁止使用香料添加剂， 传统香烟，而电子香烟有超过7,000种不同的口味。其中许多 在糖果和流行的软饮料中发现了香料，因为它们很熟悉，所以可以制造电子烟 更吸引青少年。我们假设调味剂通过以下方式增强尼古丁奖励： 感官和/或自然奖励机制。因此，调味电子烟可能会促进 尼古丁实验，依赖，最终，使用普通香烟。理解 口味如何影响电子烟的使用对于实施监管规则非常重要， 减少因消费这种日益流行的烟草而导致的潜在疾病和死亡 产品 本申请的目的是比较风味的奖励和加强性能 vs.非风味电子烟在青春期小鼠中的应用。我们的假设是，调味电子烟 奖励比非风味电子烟，风味添加剂促进和维持尼古丁 寻找青少年。第一个目标是确定甜味剂是否能增强青少年的食欲。 尼古丁奖赏和促进尼古丁自我给药。第二个目标是调查 一种可能性，一个学习的口味偏好，这模型暴露于甜的食物和饮料 在年轻的时候，将进一步增强味道诱导的尼古丁奖励和自我管理。最后我们 将确定年轻时接触调味电子烟是否会增加尼古丁的风险 成人虐待这些行为实验将由一系列分子生物学实验来补充。 调查事务所首先，我们将采用体内四极记录来测量多巴胺神经元的变化， 在暴露于调味的和非调味的电子烟尼古丁蒸气期间发射。第二，我们将在体内利用 伏安法技术定量测量多巴胺释放NAc响应 吸入有味道的电子烟蒸汽与无味道的电子烟蒸汽。第三，我们将利用最先进的方法 以确定电子烟尼古丁蒸汽是否会改变奖励的表观遗传景观- 相关的脑区，和天气水果香料具有累加或协同效应。

E-cigarettes are increasingly used by teenagers, who are particularly vulnerable to the addictive properties of nicotine. With the exclusion of menthol, the use of flavor additives has been banned from traditional cigarettes, while e-cigarettes are marketed in over 7,000 different flavors. Many of those flavors are found in candy and popular soft drinks and, because they are familiar, make e-cigarettes more appealing to adolescents. We hypothesize that flavorants enhance nicotine reward through sensory and/or natural reward mechanisms. As a consequence, flavored e-cigarettes may promote nicotine experimentation, dependence, and eventually, the use of regular cigarettes. Understanding how flavors influence e-cigarette use is important for the implementation of regulatory rules that can reduce potential disease and death deriving from the consumption of this increasingly popular tobacco product. The goal of this application is to compare the rewarding and reinforcing properties of flavored vs. non-flavored e-cigarettes in adolescent mice. Our hypothesis is that flavored e-cigarettes are more rewarding than non-flavored e-cigarettes, and that flavor additives promote and sustain nicotine seeking in adolescents. The first goal is to determine whether sweet flavorants enhance adolescent nicotine reward and promote nicotine self-administration. The second goal is to investigate the possibility that a learned flavor preference, which models exposure to sweetened food and beverages at a young age, will further enhance flavor-induced nicotine reward and self-administration. Finally, we will determine whether exposure to flavored e-cigarettes at young age increases the risk of nicotine abuse in adulthood. These behavioral experiments will be complemented by a series of molecular investigations. First, we will employ in vivo tetrode recording to measure changes in dopamine neuron firing during exposure to flavored and non-flavored e-cig nicotine vapor. Second, we will utilize in vivo voltammetry techniques to quantitatively measure dopamine release in the NAc in response to inhalation of flavored vs.unflavored e-cigarette vapors. Third, we will utilize state-of-the art approaches to determine whether e-cigarette nicotine vapor changes the epigenetic landscape of reward- associated brain areas, and weather fruit flavorants have additive or synergistic effects.