Beyond characterizing flavors: Effects of odorless constituents (sensory additives, solvents, and synthetic nicotine) on tobacco product use behaviors from adolescence to adulthood

项目摘要/摘要： 烟草产品的风味特征与增加烟草使用的起始、强化、 戒烟也很困难。烟草产品除了具有特有的风味外，还含有无味感官添加剂。 如电子烟和无烟烟草产品中的甜味剂和合成冷却剂。 因为这些化学物质是无味的，所以在目前的FDA下，它们可能不被认为是表征味道的 即使在禁止表征香精的情况下，也可以继续添加到烟草产品中。 含有不同丙烯组合的电子烟和无烟烟草的溶剂/保湿剂组成 甘醇和甘油，以及不同程度的刺激性和甜度，也可能会影响产品的观感。 此外，最近引入的某些形式的合成尼古丁也可能影响 烟草产品和改变尼古丁的使用行为。这些无味成分(甜味剂、 合成冷却剂、溶剂和合成尼古丁)对青少年和成人烟草产品的使用，特别是在 从青少年间歇使用烟草向成人持续使用烟草过渡的关键背景仍然很差 明白了。我们建议确定这些无味成分如何改变感官和成瘾 尼古丁在不同年龄的特性，以及间歇性接触含有尼古丁的产品的早期时间 成年期的尼古丁成分会改变尼古丁的使用行为。具体地说，我们将评估无味的影响 青少年和成年啮齿动物尼古丁的感官和成瘾特性的成分(目标1)。我们将使用 啮齿动物的味觉反应性和呼吸暴露试验，以确定甜味剂，冷却剂，和 溶剂调节对烟草和合成尼古丁的口腔和呼吸感觉反应 立体异构体。我们还将研究合成冷却剂对尼古丁使用行为的影响(启动， 维持、戒断、恢复)和尼古丁诱导的脑内多巴胺释放(大脑奖赏系统)。 我们将评估冷却剂、溶剂比例和尼古丁对映体对尼古丁使用的交互影响。 使用可操作蒸气自我给药的行为。此外，我们还将研究间歇性接触 青春期啮齿动物体内蒸气或口服尼古丁中的无味成分会影响成年后的尼古丁使用行为 (目标2)。我们将使用混合蒸汽被动暴露和自我管理模式以及选择饮用 评估和比较间歇性接触甜味剂和预适应甜味剂和 人工合成的冷却剂或青春期特有的味道。我们将确定是否接触到这些 添加剂改变了成年人对尼古丁的寻求、依赖、与奖励相关的行为，以及后来的大脑多巴胺释放 在生活中。我们的发现还将评估性别和年龄在无味成分对烟草影响中的作用。 使用。项目成果将向FDA提供关于无味化学品对感官的影响的信息 尼古丁的成瘾特性及其对青少年尼古丁使用向成年期转变的影响 使用。

Project Summary/Abstract: Characterizing flavors in tobacco products are associated with increased tobacco use initiation, reinforcement, and difficulty quitting. In addition to characterizing flavors, tobacco products contain odorless sensory additives such as sweeteners and synthetic cooling agents found in e-cigarettes and smokeless tobacco products. Because these chemicals are odorless, they may not be considered characterizing flavors under current FDA definitions and may continue to be added to tobacco products even when characterizing flavors are banned. Solvent/humectant composition of e-cigarettes and smokeless tobacco, with different combinations of propylene glycol and glycerol, and different levels of irritancy and sweetness, may also affect product perceptions. Moreover, certain forms of recently introduced synthetic nicotine may also affect the sensory properties of tobacco products and alter nicotine use behaviors. The effects of these odorless constituents (sweeteners, synthetic cooling agents, solvents, and synthetic nicotine) on youth and adult tobacco product use, especially in the critical context of transition from intermittent adolescent use to persistent adult tobacco use, remain poorly understood. We propose to determine how these odorless constituents alter the sensory and addictive properties of nicotine at different ages, and how early intermittent exposure to products containing these constituents alters nicotine use behaviors in adulthood. Specifically, we will assess the effects of odorless constituents on sensory and addictive properties of nicotine in adolescent and adult rodents (Aim 1). We will use rodent taste reactivity and respiratory exposure assays to determine whether sweeteners, cooling agents, and solvents modulate oral and respiratory sensory responses to tobacco-derived and synthetic nicotine stereoisomers. We will also examine the effects of synthetic cooling agents on nicotine use behaviors (initiation, maintenance, withdrawal, reinstatement) and nicotine-induced dopamine release in brain (brain reward system). We will evaluate interactive effects of cooling agents, solvent ratios, and nicotine enantiomers on nicotine use behaviors using operant vapor self-administration. In addition, we will examine how intermittent exposure to odorless constituents in vapor or oral nicotine in adolescent rodents affects nicotine use behaviors in adulthood (Aim 2). We will use a mixed vapor passive exposure and self-administration model as well as choice drinking assays to evaluate and compare the effects of intermittent exposure and preconditioning to sweetener and synthetic coolants or characterizing flavors during adolescence. We will determine whether exposure to these additives alters adult nicotine seeking, dependence, reward-related behaviors, and brain dopamine release later in life. Our findings will also evaluate the role of sex and age in the effects of odorless constituents on tobacco use. Project outcomes will provide information to the FDA about the impact of odorless chemicals on sensory and addictive properties of nicotine, and their effect on the transition from adolescent nicotine use to adulthood use.