Striatal mechanisms for e-cigarette reinforcement by flavorants

香料增强电子烟的纹状体机制

• 批准号: 10197866
• 负责人: Mariella De Biasi
• 金额: $ 58.13万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10197866
• 关键词: Address; Adolescence; Adolescent; Adult; Affect; Age; Area; Automobile Driving; Behavior; Behavioral; Biochemical; Brain; Candy; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chemical Actions; Chronic; Cigarette; Clinical Research; Consumption; Corpus striatum structure; Cues; Data; Dependence; Devices; Disease; Dopamine D2 Receptor; Dopamine Receptor; Dose; Electronic cigarette; Electrophysiology (science); Exclusion; Exposure to; Flavoring; Fostering; Friends; Fruit; Future; Genus Mentha; Goals; High School Student; Human; JUUL; Measures; Mentha spicata; Menthol; Minor; Mus; Neurons; Nicotine; Nicotine Dependence; Nicotinic Receptors; Nucleus Accumbens; Odors; Olfactory tubercle; Output; Pharmacologic Actions; Play; Policies; Property; Psychological reinforcement; Rewards; Role; Sales; Self Administration; Sensory; Slice; Smell Perception; Stimulus; Strawberries; Synapses; Synaptic plasticity; Teenagers; Testing; Time Study; Vendor; Ventral Striatum; Ventral Tegmental Area; base; cholinergic neuron; combustible cigarette; conditioned place preference; dopaminergic neuron; drug of abuse; e-cigarette aerosols; electronic cigarette use; electronic liquid; experience; experimental study; insight; mesolimbic system; nerve supply; neuronal excitability; neurophysiology; nicotine exposure; nicotine reward; nicotine seeking behavior; nicotine vapor; olfactory nuclei; optogenetics; preclinical study; preference; psychostimulant; public health relevance; reinforcer; relating to nervous system; response; reward circuitry; reward processing; sensory input; smoking cessation; soft drink; tobacco control; tobacco products; vaping; vapor; young adult

E-cigarettes are increasingly used by teenagers, who are particularly vulnerable to the addictive properties of nicotine. With the exclusion of menthol, the use of flavor additives has been banned from traditional cigarettes, while e-cigarettes (e-cigs) are marketed in over 7,000 different flavors. We hypothesize that flavorants enhance nicotine reward through sensory and/or natural reward mechanisms. As a consequence, flavored e-cigs may promote nicotine experimentation, dependence, and eventually, the use of regular cigarettes. Despite the fact that the FDA has recently regulated the sales of flavored e-cigs to minors, no flavor ban has been implemented, and adolescents could still obtain flavored e-cig products through friends or unscrupulous sellers. Furthermore, understanding how flavors influence e-cig use is important for the implementation of regulatory rules that can reduce potential disease and death deriving from the consumption of this increasingly popular tobacco product. The overall goal of this application is to compare the rewarding and reinforcing properties of flavored vs. non-flavored e-cigs in adolescent and adult mice, and identify the neural substrates responsible for the enhancing effects of flavorants. Our hypothesis is that flavored e-cigs are more rewarding than non-flavored e-cigs and that flavor additives promote and sustain nicotine seeking in adolescents due to the combined influence of flavorants and nicotine on the ventral striatum. The first goal is to determine whether flavorants enhance adolescent nicotine reward and promote nicotine self- administration, and compare their effects in adult mice. The second goal is to understand how e-cig flavorants are encoded in the ventral striatum during acquisition of e-cigarette vapor preference and self-administration. The third goal is to determine whether exposure to e-cig flavorants alters synaptic plasticity in the ventral striatum and whether it modifies cellular responses to nicotine. Our experiments will combine behavioral approaches with tetrode recordings during behavior and brain slice electrophysiology to determine how e-cigarette nicotine vapor affects reward-associated brain areas, and whether flavorants (e.g. fruit or mint) have additive or synergistic effects.

青少年越来越多地使用电子烟，他们特别容易受到上瘾的人的影响 尼古丁的特性。随着薄荷醇的排除，香料添加剂的使用已被禁止 传统香烟，而电子烟(e-cig)有超过7000种不同的口味。我们 假设香料通过感官和/或自然奖赏增强尼古丁奖赏 机制。因此，调味的电子烟可能会促进尼古丁实验，依赖， 最终，普通香烟的使用。尽管美国食品和药物管理局最近对 向未成年人销售加味电子烟，未实施调味禁令，青少年仍可 通过朋友或不法卖家获取有味道的电子烟产品。此外，了解如何 口味影响电子烟的使用对于实施监管规则很重要，可以减少 这种越来越受欢迎的烟草产品的消费可能导致疾病和死亡。 本应用程序的总体目标是比较以下各项的奖励和强化特性 在青春期和成年小鼠中进行加味和非调味电子烟的比较，并确定神经底物 负责调味剂的增强效果。我们的假设是，调味的电子烟 比非调味电子烟更有价值，香料添加剂促进和维持尼古丁的寻求 青少年由于香料和尼古丁对腹侧纹状体的联合影响。第一 目标是确定香料是否增强青少年尼古丁奖赏和促进尼古丁自身 给药，并比较它们在成年小鼠中的效果。第二个目标是了解电子烟是如何 在获得电子烟蒸气偏好的过程中，香料在腹侧纹状体中编码，并 自治。第三个目标是确定接触电子烟调味剂是否会改变突触 腹侧纹状体的可塑性以及它是否改变了细胞对尼古丁的反应。我们的实验 将在行为和大脑切片过程中将行为方法与四极管记录相结合 电生理学来确定电子烟尼古丁蒸气如何影响与奖励相关的大脑区域， 以及调味剂(如水果或薄荷)是否具有相加或协同作用。