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: 9764306
• 负责人: Nii A Addy
• 金额: $ 66.51万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9764306
• 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; Fruit; Genus Mentha; Goals; Human; Image; Inhalation; Intake; Intravenous; Knockout Mice; Knowledge; Liquid substance; 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; Work; Xylitol; addiction; cigarette smoke; conditioning; electronic cigarette use; experience; hookah; in vivo; irritation; nicotine seeking behavior; nicotine use; nicotine vapor; novel; preference; receptor; respiratory; response; snuff; sugar; sweet receptor; tobacco products; vanillin; vaping; 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 甜味和薄化烟草产品（包括精神病香烟）的使用者比例 急剧增加，尤其是在青少年人口中，引起了人们对粉丝可能有助于的担忧 烟草产品使用和促进尼古丁成瘾的倡议。另一个问题是最新的 引入可能具有类似于精神病的作用的合成冷却剂。儿童和青少年是 通过先前的经验，可以将甜味和冷却口味（水果，糖果，薄荷等）与高 甜味剂含量（糖或人造甜味剂）。但是，口味在烟草产品的倡议中的作用 在人类中，尤其是在青少年和永不使用的人中，难以研究使用。该项目的目的是使用 我们的青少年和成人啮齿动物的遗传和无烟烟草产品的使用以及口服风味的模型 尼古丁自我给药，以检查烟草产品中的甜和冷却口味是否增强尼古丁 使用行为和成瘾。我们将确定早期风味和早期风味关联是否 甜味剂会影响随后的尼古丁选择和主动性，维护和对配对尼古丁的救济 和风味摄入量。在AIM 1中，我们将检查甜味和冷却的风味和调节效果 关于尼古丁的选择和使用。在此目标中，我们将研究（a）调节对甜味和甜味的影响 尼古丁厌恶和风味偏好的冷却口味，以及（b）表征甜和冷却的影响 尼古丁的倡议和维持尼古丁寻求尼古丁的倡议和维持的风味。我们也会 使用体内伏安法检查与奖励相关的多巴胺信号反应，因为这些信号 可以用作生物标志物，以增强尼古丁使用和成瘾的能力。在AIM 2中，我们将 检查合成冷却剂对电子烟引起的呼吸刺激的影响 蒸气 - 可能有可能促进尼古丁摄入和使用的效果。这项工作的结果； （1）将提供 FDA了解甜蜜和冷却的风味对尼古丁服用的主动性和持久性的影响， （2）可以用来指导有关烟草产品中甜味和冷却口味的政策决定。