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

摘要：1号项目 甜味和薄荷烟草产品(包括薄荷香烟)的使用者比例为 急剧增加，特别是在青少年群体中，引发了人们对口味可能有助于 开始使用烟草产品并促进尼古丁成瘾。另一个令人担忧的是最近 引入可能具有类似于薄荷脑效果的合成冷却剂。儿童和青少年 根据先前的经验，有条件地将甜味和冷味(水果、糖果、薄荷等)联系起来使用高 甜味剂含量(糖或人工甜味剂)。然而，香料在烟草产品启动过程中的作用 在人类身上研究使用是困难的，特别是在青少年和从不使用的人身上。该项目的目标是使用 我们的青少年和成年啮齿动物吸入性和无烟性烟草产品的使用模型，以及口腔味道的配对模型 尼古丁自我给药，以检查烟草产品中的甜味和凉味是否增强尼古丁 使用行为和成瘾。我们将确定早期接触香料和早期香料的关系 加甜味剂会影响后续的尼古丁选择和对尼古丁的开始、维持和复发 和调味剂的摄入量。在目标1中，我们将检查甜味和凉味的暴露和调节效果。 尼古丁的选择和使用。在这个目标中，我们将研究(A)调理对甜味和 冷却口味对尼古丁厌恶和口味偏好的影响以及(B)甜味和冷却特征的影响 气味暴露对尼古丁摄取和寻求尼古丁复发的启动和维持。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调味剂的反应，因为这些信号 可以作为调味剂增加尼古丁使用和成瘾的能力的生物标志物。在目标2中，我们将 检测合成冷却剂对电子烟引起的呼吸道刺激的影响 蒸气--有可能促进尼古丁摄入和使用的效果。这项工作的成果；(1)将提供 FDA了解甜味和凉味对尼古丁摄取的开始和持续的影响， (2)可用于指导烟草产品中甜味和清凉香料的监管决策。

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.