Impact of Adding Tobacco Constituents Nornicotine and Anatabine on Self-Administered Nicotine.

添加烟草成分去甲尼古丁和新烟碱对自行服用尼古丁的影响。

• 批准号: 10018834
• 负责人: Jennifer E Murray
• 金额: $ 5.24万
• 依托单位: UNIVERSITY OF GUELPH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10018834
• 关键词: Address; Adolescent; Adult; Affinity; Agonist; Alkaloids; Behavior; Chemicals; Cigarette Smoker; Data; Dose; Drug Kinetics; Electronic Nicotine Delivery Systems; Electronic cigarette; Female; Individual; Infusion procedures; Intravenous; Investigation; Knowledge; Measures; Minor; Modeling; Motivation; Mus; Nicotine; Nicotine Dependence; Nicotinic Receptors; Outcome; Pattern; Pharmacology; Population; Property; Psychological reinforcement; Rattus; Research; Risk; Schedule; Self Administration; Time; Tobacco; Tobacco Dependence; Tobacco Use Disorder; Tobacco smoke; Tobacco use; Training; Vaporizer; Youth; acetylcholine receptor agonist; base; design; electronic vape; expectation; experimental study; innovation; interest; male; nicotine abuse; nicotine exposure; nicotine use; nornicotine; peer; receptor; reinforcer; response; smoking cessation; smoking prevalence; tobacco abuse; tobacco products; young adult

PROJECT SUMMARY/ABSTRACT The recent rise in the use of electronic nicotine delivery systems (ENDS), or e-cigarettes, is fueling interest in the relative contribution of nicotine versus constituent tobacco compounds in the abuse liability of tobacco products. Originally designed to be used as smoking cessation aids, these nicotine vaporizers are being marketed as safe alternatives to tobacco with a dizzying array of available flavors and levels of nicotine content. Because of the wide misconception that use of ENDS is not harmful because tobacco is not burned, there is a gradually-emerging population who are initiating their nicotine addiction by ‘vaping’ these ENDS rather than through actual tobacco products. This population is therefore pre-exposed to nicotine, and may be at subsequent greater risk for tobacco dependence. Indeed, there is early evidence that those individuals who begin consuming nicotine in ENDS form have a greater chance of transitioning to tobacco consumption than their never-using peers. The interactions between nicotine and constituent tobacco compounds have not yet been addressed in the context of this enhanced risk of tobacco abuse following nicotine pre-exposure. The objective of this research is to fill that scientific gap by assessing the impact of the addition of constituent compounds to nicotine in an intravenous self-administration model in male and female adult and adolescent rats. In Aim 1, nornicotine and anatabine will be added to self-administered nicotine in adults; in Aim 2, nornicotine and anatabine will be added to self-administered nicotine in adolescents. In both Aims, we will assess the impact of the added constituent compound on the motivational value of nicotine. The effect of adding a constituent compound in each Aim is expected to reduce simple self- administration because their agonist actions at nicotinic acetylcholine receptors provides a level of nicotine substitution. However, nornicotine, but not anatabine, has also been shown to have reinforcing properties, likely due to its far greater relative affinity for α4β2* receptors. Therefore, nornicotine, but not anatabine, is expected to enhance the motivational value of nicotine as measured by repeated sessions on a progressive ratio schedule because of this additive reinforcement value. A differential impact of the addition of constituent compounds to nicotine will provide a unique perspective on the tenacity of tobacco dependence. Indeed, current investigations of the impact of tobacco constituent compounds on nicotine abuse liability revolve around regulatory research focused on the effects of reducing nicotine content in tobacco. The current study, however, will investigate the relative contribution of nicotine versus constituent tobacco compounds on the abuse liability of tobacco products from the perspective of this emerging population who begin their nicotine use with ENDS rather than tobacco. This conceptually innovative approach incorporating pharmacological manipulations with motivational assessments using repeated progressive ratio schedules will allow us to begin to address a problem that is only likely to grow with time.

项目概要/摘要 最近电子尼古丁输送系统（ENDS）或电子烟的使用增加，引发了人们对电子尼古丁输送系统（ENDS）或电子烟的兴趣。 尼古丁与烟草成分在烟草滥用倾向中的相对贡献 产品。这些尼古丁蒸发器最初设计用作戒烟辅助工具，现在正在 作为烟草的安全替代品销售，具有一系列令人眼花缭乱的可用口味和尼古丁含量水平。 由于人们普遍错误地认为使用电子尼古丁传送系统并无害处，因为烟草并未燃烧，因此存在一种 逐渐出现的人群通过“吸食”这些电子烟而不是开始尼古丁成瘾 通过实际的烟草产品。因此，该人群预先暴露于尼古丁，并且可能处于 随后出现更大的烟草依赖风险。事实上，有早期证据表明，那些 开始消费 ENDS 形式的尼古丁比消费烟草更有可能转变为烟草消费 他们从不使用的同伴。尼古丁和烟草成分之间的相互作用尚未确定 在尼古丁预暴露后烟草滥用风险增加的背景下得到了解决。这 这项研究的目的是通过评估添加的影响来填补这一科学空白 男性和女性静脉自我给药模型中尼古丁的组成化合物 雌性成年和青少年大鼠。在目标 1 中，自我给药中将添加去甲尼古丁和新烟草碱 成人尼古丁；在目标 2 中，将在自我管理的尼古丁中添加去甲尼古丁和新烟碱 青少年。在这两个目标中，我们将评估添加的成分化合物对动机的影响 尼古丁的价值。在每个目标中添加组成化合物的效果预计会减少简单的自 给药，因为它们对烟碱乙酰胆碱受体的激动作用提供了一定水平的尼古丁 替代。然而，降烟碱（而不是新烟草碱）也被证明具有增强特性， 可能是由于其对 α4β2* 受体的相对亲和力要大得多。因此，降烟碱，而不是新烟草碱，是 预计将提高尼古丁的激励价值（通过按渐进比例重复进行测量） 由于这种附加强化值而安排。添加成分的不同影响 尼古丁化合物将为研究烟草依赖的顽固性提供独特的视角。的确， 目前关于烟草成分化合物对尼古丁滥用倾向的影响的调查围绕 围绕减少烟草中尼古丁含量的影响的监管研究。目前的研究， 然而，我们将研究尼古丁与烟草成分对烟碱的相对贡献 从开始使用尼古丁的新兴人群的角度来看烟草制品的滥用倾向 与电子尼古丁传送系统（ENDS）一起使用，而不是与烟草一起使用。这种概念上的创新方法结合了药理学 使用重复渐进比率表进行动机评估的操作将使我们能够开始 解决一个可能随着时间的推移而加剧的问题。