Electronic cigarettes, adolescents, and changes in neurobiology

电子烟、青少年和神经生物学的变化

• 批准号: 10399991
• 负责人: Brandon Jarrod Henderson
• 金额: $ 37.53万
• 依托单位: MARSHALL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10399991
• 关键词: Addictive Behavior; Address; Adolescent; American; Americas; Antibodies; Ants; Basic Science; Behavior; Behavioral; Biological Assay; Biological Models; Brain; Brain region; Cells; Communities; Complement; Data; Devices; Disease; Dopamine; Dose; Drosophila acetylcholine receptor alpha-subunit; Electrochemistry; Electronic Nicotine Delivery Systems; Electronic cigarette; Electrophysiology (science); Exhibits; Face; Flavoring; Fluorescence Microscopy; Formulation; Generations; Goals; Human; JUUL; Knowledge; Lead; Link; Measures; Menthol; Methods; Modeling; Mus; National Institute of Drug Abuse; Neurobiology; Nicotine; Nicotine Dependence; Outcome; Pathway interactions; Periodicity; Policies; Population; Prefrontal Cortex; Psychological reinforcement; Public Health; Research; Rewards; Risk; Role; Salts; Scanning; Self Administration; Smoker; Sodium Chloride; System; Testing; Tweens; Up-Regulation; addiction; base; brain cell; cell type; combustible cigarette; dopaminergic neuron; electronic liquid; electronic vape; high risk population; in vivo Model; innovation; interest; mouse model; neuronal excitability; neurophysiology; neurotransmission; nicotine reward; nicotine use; novel; patch clamp; prenatal; preventable death; smoking initiation; success; tobacco products; vaper; vaping; vaping nicotine; vapor

Project Summary/Abstract There is a fundamental gap in the understanding of how electronic nicotine delivery systems (ENDS) al- ter the adolescent brain. Adolescents are a high-risk population in regards to nicotine-containing products as prenatal or early exposure triggers significant changes in the prefrontal cortex. With the growing popularity of ENDS among American adolescents, there is a critical need to understand how ENDS devices alter neurobiol- ogy to trigger addiction to nicotine. This is especially true given that ENDS are unique from combustible ciga- rettes given the multitude of flavors and different nicotine formulations that are specific to only ENDS e-liquids. Additionally, pod-based ENDS (i.e., Juul) contain a significantly higher concentration of nicotine compared to combustible cigarettes and tank-based ENDS. Until this knowledge gap is closed, we face the risk of increased smoking initiation, decreased cessation, and a cumulative effect of a growing population of lifelong smokers in America. Our overall goal is to identify the key changes in neurobiology, specific to ENDS, in an adolescent mouse model system that regulates nicotine reward and reinforcement. To address this, we will utilize a novel contingent nicotine self-administration assay system that allows us to use the same e-liquid tanks and Pods popular with adolescent ENDS users in a mouse model system. This will provide high translational value as we can directly assess how ENDS directly alter neurobiology and neurophysiology. We hypothesize that directly linking self-administration behavior to nAChR upregulation and changes in neurophysiology will identify brain regions and cell-types that are critical for the initiation of nicotine addiction and continued reinforcement. The rationale behind this comes from the applicant’s previous success in corre- lating nicotine reward to nAChR upregulation. We will identify ENDS-specific changes in neurobiology with three specific aims. First, we will utilize e-Vape nicotine self-administration assays in mice to examine initiation and nicotine reinforcement of ENDS to examine the impact of nicotine dose, formulation, and flavors on vap- ing-related behavior. Second, we will use the brains from the first aim to examine nAChR upregulation and provide a direct link between self-administration behavior and nAChR upregulation. Third, we will examine changes in neurophysiology via electrophysiology and fast-scan cyclic voltammetry. This approach is innovative, in the applicant's opinion, because it establishes a direct correlation be- tween vaping-related self-administration and nAChR upregulation as well as changes in neurophysiology in an in vivo model and utilizes the exact same ENDS and e-liquids popular with human adolescent vapers. This is complemented by the use of a novel mouse expressing α4-mCherry and α6-GFP nAChR subunits that allow analysis of upregulation without the use of antibodies. The proposed research is significant, because it will dramatically increase our knowledge of how ENDS contribute to addictive behavior. This would contribute sig- nificantly to several of the priorities and interests of NIDA.

项目摘要/摘要 理解电子尼古丁输送系统（末端）al-存在根本差距 青春期大脑。对于含尼古丁的产品而言，青少年是高风险的人口 产前或早期暴露会触发前额叶皮质的重大变化。随着日益普及 在美国青少年中结束时，迫切需要了解端设备如何改变神经生物醇 - OGY触发尼古丁的成瘾。尤其如此，尤其是，混合的烟气是独一无二的 重新考虑到仅特定于末端液体的多种口味和不同的尼古丁公式。 此外，基于POD的末端（即JUUL）含有与 可燃文明和基于坦克的目的。在封闭这些知识差距之前，我们面临增加的风险 吸烟启动，停止减少以及终身吸烟者越来越多的累积作用 美国。我们的总体目标是在青少年中确定特定于目的的神经生物学的关键变化 调节尼古丁奖励和增强的鼠标模型系统。为了解决这个问题，我们将利用一本小说 一定的尼古丁自加入测定系统，使我们能够使用相同的电子液体储罐和豆荚 在鼠标模型系统中，青少年端用户很受欢迎。这将为我们提供高度的翻译价值 可以直接评估末端如何直接改变神经生物学和神经生理学。 我们假设将自我管理行为与NACHR上调和变化直接联系起来 神经生理学将确定对尼古丁成瘾至关重要的大脑区域和细胞类型 并继续加强。这背后的理由来自申请人以前在Corre中的成功 将尼古丁奖励奖励nachr上调。我们将通过 三个具体目标。首先，我们将在小鼠中利用E-vape Nicotine自我管理测定法进行检查 以及尼古丁的末端增强，以检查尼古丁剂量，配方奶粉和口味对VAP的影响 与Ing相关的行为。其次，我们将使用第一个目的的大脑检查NACHR上调和 提供自我管理行为与NACHR上调之间的直接联系。第三，我们将检查 通过电生理学和快速扫描环状伏安法的神经生理学变化。 申请人认为，这种方法具有创新性，因为它建立了直接相关性 推文与蒸发相关的自我管理和NACHR上调以及神经生理学的变化 体内模型并利用完全相同的末端和电子液体在人类青少年蒸气中流行。这是 通过使用一种新型小鼠表达α4-MCHERRY和α6-GFP NACHR亚基来完成 分析上调无抗体。拟议的研究很重要，因为它将 动态地增加我们对目的的知识有助于其他行为。这将有助于sig- NIDA的几个优先事项和利益。