Assessing the effects of adolescent nicotine vapor exposure on motivation and decision for rewards

项目摘要 缺乏信息，加上有针对性的广告，增加了可口的味道，以及误解 对其安全性的担忧导致电子尼古丁递送系统(e- 香烟)，电子烟销售额从2008年的2000万美元上升到2014年的15亿美元。在青少年中， 电子烟的年使用量持续增长尤其高，现在电子烟的使用量 在这一人群中超过了传统香烟。青春期大脑的神经生物学 产生一种行为表型，增加寻求奖励的行为，并使他们从事 更冲动、更危险的行为，包括实验性吸毒。这些发现证明了一个关键的 需要就尼古丁蒸气暴露对青少年健康的影响进行更多研究，包括其 对可塑性青春期大脑及其控制的行为的影响。我们假设青少年 暴露在尼古丁蒸气中会导致寻求奖励行为的长期戏剧性变化。基于 调查尼古丁对决策和暗示的影响的有限数量的研究结果-- 诱导奖励动机，我们预测反复暴露在尼古丁蒸气中将导致 冲动选择显著增加，风险性选择减少，线索选择减少。 雄性和雌性大鼠的奖赏寻求行为的诱导增强。此外，我们预计 特定的烟碱受体亚型，特别是纹状体中的烟碱受体亚型，将预测奖励选择和 动力。我们将使用成本效益决策和巴甫洛夫比法来检验这些预测 以食物颗粒为奖励的仪器转移测试。这项研究的目标是确定 青春期接触尼古丁蒸气会导致冲动或危险的长期显著变化 选择(目标1a)或奖励配对线索能力的长期变化，以激励奖励寻求 行为(目标1b)。此外，奖赏动机或奖赏选择与尼古丁的关系 有或无尼古丁蒸气或青春期烟雾的大鼠脑内α-4-β-2受体水平 暴露，将被确定(目标2)。这项研究将提供即时和急需的信息 关于这种在青少年中常见的上升的和潜在的破坏性成瘾趋势。

Project Summary A lack of information, along with targeted advertising, addition of palatable flavors, and misconceptions about their safety has led to a dramatic increase in the use of electronic nicotine delivery systems (e- cigarettes), with sales of e-cigarettes rising from $20 million in 2008 to $1.5 billion in 2014. In adolescents, continuing annual increases in e-cigarette use have been particularly high and e-cigarette use has now surpassed that of traditional cigarettes within this population. The neurobiology of the adolescent brain produces a behavioral phenotype that increases reward-seeking behavior and makes them engage in more impulsive and risky behaviors, including experimental drug use. These findings warrant a critical need for more research on the effects of nicotine vapor exposure on adolescent health, including its effects on the malleable adolescent brain and the behavior that it controls. We posit that adolescent exposure to nicotine vapor results in long-term dramatic changes in reward seeking behaviors. Based on the results of a limited number of studies investigating the effects of nicotine on decision making and cue- induced motivation for rewards, we predicted that repeated exposure to nicotine vapor will cause a significant and persist increases in impulsive choice, decreases in risky choice, and decreases in cue- induced potentiation of reward seeking behavior, in both male and female rats. Additionally, we expect that specific nicotinic receptor subtypes, particularly within the striatum, will predict reward choice and motivation. We will test these predictions using cost-benefit decision making and Pavlovian-to- Instrumental Transfer tests with food pellets as the reward. The goal of this research is to determine if exposure to nicotine vapor during adolescence causes significant long-term changes in impulsive or risky choice (Aim 1a) or long-term changes in the ability of reward paired cues to invigorate reward seeking behavior (Aim 1b). Additionally, relationships between reward motivation or reward choice and nicotinic α4β2 receptor levels in the brains of rats, with and without a history or adolescent nicotine vapor exposure, will be determined (Aim 2). This research will provide immediate and much needed information about this rising and potentially devastating addictive trend, commonly observed in adolescents.