Comparative neurobehavioral pharmacology of combusted and non-combusted tobacco products

燃烧和未燃烧烟草产品的神经行为药理学比较

基本信息

项目摘要

SUMMARY The purpose of this project is to identify mechanisms mediating the differential abuse liability of combusted cigarettes versus non-combusted tobacco products. Conventional tobacco cigarettes have greater abuse liability than non-combusted products such as electronic cigarettes (ECs), smokeless tobacco, and nicotine replacement therapy (NRT). To date, data from animal studies of exposure to extracts of commercial tobacco products that contain nicotine and a range of non-nicotine tobacco constituents appear to be consistent with the greater abuse liability of combusted products observed in humans. The mechanisms mediating the greater abuse liability of combusted products remain unclear, but may reflect the unique or higher levels of addiction- relevant non-nicotine constituents in cigarette smoke (CS). Some of these constituents (e.g., volatile organic compounds, monoamine oxidase (MAO) inhibitors) can mimic or enhance the effects of nicotine, or can exhibit abuse liability themselves. This project will compare the addiction-related behavioral and neurobiological effects of CS extract, EC aerosol extract, and nicotine alone (NRT analog). Importantly, CS extract will contain both water- and non-water-soluble constituents from both the particulate and gas phase of CS, thereby providing the most comprehensive CS extract ever used in preclinical addiction studies. Levels of a range of behaviorally relevant non-nicotine constituents in the extracts will be measured to identify specific constituents that may be responsible for observed differences in abuse liability. Our general hypothesis is that CS extract will have greater addiction-related behavioral and neurobiological effects than the other formulations due to its higher levels of behaviorally active non-nicotine constituents. Aim 1 will compare the addiction-related neurobiological and pharmacokinetic effects of CS extract, EC extract and nicotine alone, including binding affinity and functional activity at a wide range of addiction-related receptors in vitro, ability to up-regulate nicotinic acetylcholine receptors, produce MAO inhibition, and induce c-fos expression in addiction-related brain areas ex vivo, ability to elicit dopamine and serotonin release in the nucleus accumbens in vivo, and nicotine pharmacokinetics. Aim 2 will compare the reinforcement-enhancing and aversive effects of formulations using intracranial self-stimulation, as well as their effects on ex vivo neural measures under these dosing conditions. Aim 3 will compare the relative elasticity of demand for (reinforcing efficacy of) formulations using self-administration methods when each formulation is available in isolation and under novel choice procedures where each extract is available concurrently with nicotine to examine substitutability. This project will provide the first direct comparison of both the addiction-related behavioral and neurobiological effects of different classes of tobacco products, and will significantly advance our understanding of the basic neurobiological mechanisms underlying the differential abuse liability between them. As such, this work may inform development of better medications for tobacco addiction by tailoring them to different product classes.
总结

项目成果

期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Stimulus functions of nicotine.
Dose- and Sex-Dependent Bidirectional Relationship between Intravenous Fentanyl Self-Administration and Gut Microbiota.
  • DOI:
    10.3390/microorganisms10061127
  • 发表时间:
    2022-05-30
  • 期刊:
  • 影响因子:
    4.5
  • 作者:
    Ren, Michelle;Lotfipour, Shahrdad
  • 通讯作者:
    Lotfipour, Shahrdad
Sex- and Genotype-Dependent Nicotine-Induced Behaviors in Adolescent Rats with a Human Polymorphism (rs2304297) in the 3'-UTR of the CHRNA6 Gene.
Unique effects of nicotine across the lifespan.
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ANDREW Charles HARRIS其他文献

ANDREW Charles HARRIS的其他文献

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{{ truncateString('ANDREW Charles HARRIS', 18)}}的其他基金

Comparative neurobehavioral pharmacology of combusted and non-combusted tobacco products
燃烧和未燃烧烟草产品的神经行为药理学比较
  • 批准号:
    10206086
  • 财政年份:
    2020
  • 资助金额:
    $ 64.18万
  • 项目类别:
Comparative neurobehavioral pharmacology of combusted and non-combusted tobacco products
燃烧和未燃烧烟草产品的神经行为药理学比较
  • 批准号:
    10413953
  • 财政年份:
    2020
  • 资助金额:
    $ 64.18万
  • 项目类别:
Animal models to inform FDA tobacco regulation: Assessing the relative abuse liability of different classes of tobacco products
为 FDA 烟草监管提供信息的动物模型:评估不同类别烟草产品的相对滥用倾向
  • 批准号:
    9770827
  • 财政年份:
    2018
  • 资助金额:
    $ 64.18万
  • 项目类别:
Animal models for evaluating the relative abuse liability of electronic cigarettes
评估电子烟相对滥用倾向的动物模型
  • 批准号:
    9130342
  • 财政年份:
    2016
  • 资助金额:
    $ 64.18万
  • 项目类别:
Compensation of Nicotine Self-Administration
尼古丁自我给药的补偿
  • 批准号:
    7273382
  • 财政年份:
    2007
  • 资助金额:
    $ 64.18万
  • 项目类别:

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