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

项目概要/摘要： 烟草制品中的特征性风味与烟草使用的开始、强化 很难戒掉。除了特征性的香料，烟草产品还含有无味的感官添加剂 例如电子烟和无烟烟草产品中的甜味剂和合成清凉剂。 由于这些化学物质是无味的，因此根据当前FDA的规定， 定义，并可能继续添加到烟草产品，即使特征香料被禁止。 电子烟和无烟烟草的溶剂/湿润剂组合物，具有丙烯的不同组合 乙二醇和甘油以及不同程度的刺激性和甜味也可能影响产品的感觉。 此外，最近引入的某些形式的合成尼古丁也可能影响烟草的感官特性。 烟草制品和改变尼古丁使用行为。这些无味成分（甜味剂， 合成清凉剂、溶剂和合成尼古丁）对青少年和成人烟草产品使用的影响，特别是在 从间歇性青少年吸烟过渡到持续性成人吸烟的关键背景仍然很差 明白我们建议确定这些无味成分如何改变感官和成瘾性 尼古丁在不同年龄的特性，以及如何早期间歇性暴露于含有这些产品 尼古丁成分会改变成年人的尼古丁使用行为。具体来说，我们将评估无气味的影响， 尼古丁在青少年和成年啮齿动物中的感觉和成瘾特性（目的1）。我们将使用 啮齿动物味觉反应性和呼吸暴露测定，以确定甜味剂、清凉剂和 溶剂调节对烟草衍生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（开始， 维持、戒断、恢复）和尼古丁诱导的脑中多巴胺释放（脑奖励系统）。 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作用 使用操作性蒸汽自我管理的行为。此外，我们还将研究间歇性暴露于 青少年啮齿动物尼古丁蒸气或口服尼古丁中的无味成分影响成年后的尼古丁使用行为 (Aim 2）。我们将使用混合蒸汽被动暴露和自我管理模型以及选择饮用水 评价和比较间歇性暴露和预处理对甜味剂的影响的测定， 在青春期使用合成的清凉剂或特征性的香料。我们将确定是否暴露于这些 添加剂改变成人尼古丁寻求，依赖，奖励相关行为和大脑多巴胺释放 生活中我们的研究结果也将评估性别和年龄在无臭成分对烟草影响中的作用 使用.项目成果将为FDA提供有关无味化学品对感官影响的信息。 尼古丁的成瘾特性，以及它们对青少年尼古丁使用向成年过渡的影响 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.