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Striatal mechanisms for e-cigarette reinforcement by flavorants

香料增强电子烟的纹状体机制

基本信息

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
项目类别：
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

项目摘要

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.

越来越多的青少年使用电子烟，他们特别容易上瘾