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

摘要：项目#1 甜味和薄荷烟草产品（包括薄荷香烟）的使用者比例 急剧增加，特别是在青少年人群中，引起了人们对口味可能有助于 开始使用烟草制品，促进尼古丁成瘾。另一个令人关切的问题是， 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 条件反射，通过先前的经验，将甜味和清凉味（水果，糖果，薄荷等）联系起来。高 甜味剂含量（糖或人工甜味剂）。然而，香料在烟草产品引发中的作用 在人类中，特别是在青少年和从未使用过的人中，很难进行研究。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的使用，以及口腔口味配对 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。我们将确定是否早期的风味暴露和早期的风味关联 甜味剂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，我们将研究甜味和清凉味的暴露和调节作用 尼古丁的选择和使用为此，我们将研究（A）调节对甜味的影响， 清凉风味对尼古丁厌恶和风味偏好的影响，以及（B）表征甜味和清凉风味的影响 香味暴露对尼古丁摄入的起始和维持以及尼古丁寻求的复发的影响。我们还将 使用体内伏安法来检查奖励相关的多巴胺信号对香料的反应，因为这些信号 可以作为香料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 检查合成冷却剂对电子烟引起的呼吸道刺激的影响 蒸汽--可能促进尼古丁摄入和使用的作用。这项工作的结果;（1）将提供 FDA了解甜味和清凉味对尼古丁摄入的起始和持续的影响， （2）可用于指导烟草制品中甜味剂和凉味剂的调控决策。

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.