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
- 批准号:10627919
- 负责人:
- 金额:$ 64.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-15 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AffinityAnimalsAreaAttenuatedBehavioralBehavioral ModelBindingBiological AssayBrainChemicalsCigaretteDevelopmentDopamineDoseDrug KineticsElasticityElectronic cigaretteExhibitsExposure toFOS geneFormulationGasesHumanIn VitroLiquid substanceMeasuresMediatingMethodsMonoamine OxidaseMonoamine Oxidase InhibitorsNeurobiologyNicotineNicotinic ReceptorsNucleus AccumbensOutcomeParticulatePharmaceutical PreparationsPharmacologyPharmacotherapyPhasePreventionProceduresPsychological reinforcementResearchSelf AdministrationSelf StimulationSerotoninSmokeless TobaccoTobaccoTobacco DependenceTobacco useWaterWorkabuse liabilityaddictionanaloganimal datacigarette smokecomparativee-cigarette aerosolsin vivomonoamineneuralneurobehavioralneurobiological mechanismnicotine replacementnovelpre-clinicalreceptortobacco productsvolatile organic compound
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)
Antibiotic Knockdown of Gut Bacteria Sex-Dependently Enhances Intravenous Fentanyl Self-Administration in Adult Sprague Dawley Rats.
- DOI:10.3390/ijms24010409
- 发表时间:2022-12-27
- 期刊:
- 影响因子:5.6
- 作者:
- 通讯作者:
Stimulus functions of nicotine.
- DOI:10.1016/bs.apha.2021.11.001
- 发表时间:2022
- 期刊:
- 影响因子:0
- 作者:LeSage, Mark G
- 通讯作者:LeSage, Mark G
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.
- DOI:10.3390/ijms23063145
- 发表时间:2022-03-15
- 期刊:
- 影响因子:5.6
- 作者:Cardenas A;Bai Y;Hajy Heydary Y;Li J;Leslie FM;Lotfipour S
- 通讯作者:Lotfipour S
Unique effects of nicotine across the lifespan.
- DOI:10.1016/j.pbb.2022.173343
- 发表时间:2022-03
- 期刊:
- 影响因子:0
- 作者:Ren M;Lotfipour S;Leslie F
- 通讯作者:Leslie F
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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:
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