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

除了表征风味之外：无气味成分（感官添加剂、溶剂和合成尼古丁）对从青春期到成年的烟草产品使用行为的影响

• 批准号: 10666235
• 负责人: Nii A Addy
• 金额: $ 63.85万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666235
• 关键词: Address; Adolescence; Adolescent; Adult; Affect; Age; Behavior; Biological Assay; Biological Markers; Brain; Calcium; Chemicals; Cigar; Cigarette; Data; Dependence; Dopamine; Electronic cigarette; Exposure to; Foundations; Glycerol; Human Cloning; Ice; Intake; Irritants; Life; Link; Maintenance; Measures; Menthol; Mission; Modeling; Mus; Nicotine; Odors; Oral; Outcome; Perception; Plethysmography; Prevalence Study; Property; Propylene Glycols; Psychological reinforcement; Public Health; Rattus; Rewards; Rodent; Role; Self Administration; Sensory; Smokeless Tobacco; Solvents; Stereoisomer; Sweetening Agents; System; Taste Buds; Taste Perception; Testing; Tobacco; Tobacco use; Withdrawal; Youth; addiction; cigarillos; conditioning; drinking; electronic liquid; enantiomer; genetic approach; irritation; neurochemistry; nicotine reward; nicotine seeking behavior; nicotine use; nicotine vapor; oral sensory; preconditioning; preference; receptor; respiratory; response; sex; sugar; sweet taste perception; tobacco flavor; tobacco products; vanillin; vapor

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.

项目摘要/摘要： 烟草产品中的特征风味与烟草使用的起始、强化、 和戒烟困难。除了表征风味外，烟草产品还含有无味感官添加剂 例如电子烟和无烟烟草产品中的甜味剂和合成清凉剂。 由于这些化学物质无味，因此根据当前 FDA 的规定，它们可能不被视为风味特征 即使在禁止描述风味的情况下，也可能继续将其添加到烟草产品中。 电子烟和无烟烟草的溶剂/保湿剂组合物，具有不同的丙烯组合 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知。 此外，最近引入的某些形式的合成尼古丁也可能影响烟油的感官特性。 烟草制品并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，尤其是在 从青少年间歇性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性 不同年龄段尼古丁的特性，以及如何早期间歇性接触含有这些物质的产品 成分会改变成年后的尼古丁使用行为。具体来说，我们将评估无味的效果 尼古丁成分对青少年和成年啮齿动物的感官和成瘾特性的影响（目标 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。我们还将研究合成清凉剂对尼古丁使用行为（开始、 维持、戒断、恢复）和尼古丁诱导的大脑中多巴胺释放（大脑奖励系统）。 我们将评估清凉剂、溶剂比例和尼古丁对映体对尼古丁使用的相互作用影响 使用操作蒸气自我管理的行为。此外，我们将研究如何间歇性暴露于 青少年啮齿动物蒸气或口腔尼古丁中的无味成分影响成年后的尼古丁使用行为 （目标 2）。我们将使用混合蒸气被动暴露和自我管理模型以及选择饮用 评估和比较间歇性暴露和预处理对甜味剂和 合成冷却剂或青春期特征风味。我们将确定是否暴露于这些 添加剂会改变成人的尼古丁寻求、依赖、奖励相关行为以及大脑多巴胺的释放 在生活中。我们的研究结果还将评估性别和年龄在无气味成分对烟草的影响中的作用 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 尼古丁的成瘾特性及其对青少年尼古丁使用到成年过渡的影响 使用。