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

项目摘要 缺乏信息，沿着有针对性的广告，增加可口的口味，以及误解 关于它们的安全性，导致电子尼古丁输送系统（e- 电子烟的销售额从2008年的2000万美元上升到2014年的15亿美元。在青少年中， 电子烟使用的持续年度增长特别高，电子烟的使用现在 在这一人群中超过了传统香烟。青少年大脑的神经生物学 产生了一种行为表型，增加了寻求奖励的行为， 更冲动和危险的行为，包括实验性的药物使用。这些发现证明了一个关键的 需要更多的研究尼古丁蒸汽暴露对青少年健康的影响，包括其 对可塑性较强的青少年大脑及其控制的行为的影响。我们把那个青少年 暴露于尼古丁蒸汽导致奖赏寻求行为的长期显著变化。基于 研究尼古丁对决策和提示的影响的研究数量有限， 诱导奖励的动机，我们预测，反复暴露于尼古丁蒸汽将导致 冲动选择显著且持续增加，风险选择减少，线索选择减少。 在雄性和雌性大鼠中诱导增强奖赏寻求行为。此外，我们预计 特定的烟碱受体亚型，特别是在纹状体内，将预测奖励选择， 动机我们将使用成本效益决策和巴甫洛夫- 以食物颗粒作为奖励的仪器转移测试。这项研究的目的是确定， 青少年时期暴露于尼古丁蒸汽会导致冲动或冒险行为的显著长期变化。 选择（目标1a）或奖励配对线索激发奖励寻求能力的长期变化 行为（目标1b）。此外，奖励动机或奖励选择与尼古丁 大鼠大脑中α4β2受体水平，有和没有尼古丁史或青少年尼古丁蒸汽 将确定暴露（目标2）。这项研究将提供即时和急需的信息 这是一种在青少年中普遍存在的上升的、具有潜在破坏性的成瘾趋势。

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.