Research Project 1 : Effects of Sweet and Coolant Flavors on Nicotine Choice, Consumption and Seeking

研究项目 1：甜味和清凉味对尼古丁选择、消费和寻求的影响

• 批准号: 10242018
• 负责人: Nii A Addy
• 金额: $ 70.03万
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242018
• 关键词: Address; Adolescence; Adolescent; Adult; Aldehydes; Artificial Sweeteners; Aversive Stimulus; Behavior; Benzaldehyde; Biological Markers; Brain; Calcium; Candy; Categories; Child; Cigar; Cigarette; Complement; Consumption; Development; Dopamine; Electronic cigarette; Enhancers; Exposure to; Family Smoking Prevention and Tobacco Control Act; Flavoring; Fruit; Genus Mentha; Goals; Human; Image; Inhalation; Intake; Intravenous; Knockout Mice; Knowledge; Maintenance; Masks; Measures; Mediating; Menthol; Mission; Modeling; Mouse Strains; Mus; Nicotine; Nicotine Dependence; Nicotinic Receptors; Oral; Peripheral; Plethysmography; Policies; Population; Procedures; Psychological reinforcement; Rattus; Regulation; Relapse; Research Project Grants; Rewards; Rodent Model; Role; Saccharin; Self Administration; Signal Transduction; Smokeless; Smokeless Tobacco; Sweetening Agents; Testing; Tobacco use; Work; Xylitol; addiction; cigarette smoke; conditioning; e-cigarette aerosols; electronic cigarette use; electronic liquid; electronic vape; experience; hookah; in vivo; irritation; nicotine seeking behavior; nicotine use; nicotine vapor; non-cigarette tobacco product; novel; preference; receptor; respiratory; response; snuff; sugar; sweet receptor; tobacco flavor; tobacco products; vanillin; vapor

Abstract: Project #1 The proportion of users of sweet-flavored and mentholated tobacco products (including menthol cigarettes) has increased dramatically, especially within the adolescent population, raising concerns that flavors may facilitate the initiation of tobacco product use and promote nicotine addiction. An additional concern is the recent introduction of synthetic cooling agents that may have effects similar to menthol. Children and adolescents are conditioned, through prior experience, to associate sweet and cooling flavors (fruit, candy, mints, etc.) with high sweetener content (sugar or artificial sweeteners). However, the role of flavors in the initiation of tobacco product use is difficult to study in humans, especially in adolescents and never-users. The goal of this project is to use our adolescent and adult rodent models of inhaled and smokeless tobacco product use, and of oral flavor-paired nicotine self-administration, to examine whether sweet and cooling flavors in tobacco products enhance nicotine use behavior and addiction. We will determine whether early flavor exposure and early flavorant associations with sweeteners influence subsequent nicotine choice and initiation, maintenance, and relapse to paired nicotine and flavorant intake. In Aim 1, we will examine sweet and cooling flavor exposure and conditioning effects on nicotine choice and use. In this aim, we will examine (A) the effects of conditioning to sweet flavors and cooling flavors on nicotine aversion and flavor preference and (B) the effects of characterizing sweet and cooling flavor exposure on the initiation and maintenance of nicotine-taking and relapse to nicotine-seeking. We will also use in-vivo voltammetry to examine reward-related dopamine signaling responses to flavorants, as these signals could serve as a biomarker for the ability of flavorants to enhance nicotine use and addiction. In Aim 2, we will examine the effects of synthetic cooling agents on respiratory irritation caused by electronic cigarette vapors – effects that could potentially facilitate nicotine intake and use. The results of this work; (1) will provide the FDA with understanding of sweet and cooling flavor effects on the initiation and persistence of nicotine taking, and (2) could be used to guide policy decision on the regulation of sweet and cooling flavors in tobacco products.

摘要：项目#1 甜味和薄荷味烟草制品（包括薄荷醇卷烟）的使用者比例 急剧增加，特别是在青少年群体中，引起人们对口味可能会促进 开始使用烟草产品并促进尼古丁成瘾。另外一个值得关注的问题是最近 引入可能具有类似于薄荷醇效果的合成清凉剂。儿童和青少年是 通过先前的经验，将甜味和清凉味（水果、糖果、薄荷糖等）与高浓度联系起来。 甜味剂含量（糖或人造甜味剂）。然而，香料在烟草产品引发中的作用 很难研究人类的使用情况，尤其是青少年和从未使用过的人。该项目的目标是使用 我们的青少年和成年啮齿动物模型的吸入和无烟烟草产品使用以及口腔调味配对模型 尼古丁自我给药，检查烟草产品中的甜味和清凉味是否会增强尼古丁 使用行为和成瘾。我们将确定早期风味暴露和早期风味剂关联是否 甜味剂会影响随后的尼古丁选择以及配对尼古丁的开始、维持和复发 和食用香料的摄入量。在目标 1 中，我们将检查甜味和清凉风味的暴露和调理效果 关于尼古丁的选择和使用。为此，我们将研究 (A) 调理对甜味和风味的影响 清凉风味对尼古丁厌恶和风味偏好的影响以及 (B) 甜味和清凉特征的影响 风味暴露对尼古丁摄入的开始和维持以及尼古丁寻求复发的影响。我们还将 使用体内伏安法来检查与奖励相关的多巴胺信号对食用香料的反应，因为这些信号 可以作为调味剂增强尼古丁使用和成瘾能力的生物标志物。在目标 2 中，我们将 检查合成清凉剂对电子烟引起的呼吸道刺激的影响 蒸气——可能促进尼古丁摄入和使用的影响。这项工作的成果； (1) 将提供 FDA 了解甜味和清凉风味对尼古丁摄入的起始和持续性的影响， (2) 可用于指导烟草制品中甜味和清凉香料监管的政策决策。