Characterization of menthol's effect on nicotine reward and nicotinic receptor neurobiology

薄荷醇对尼古丁奖赏和烟碱受体神经生物学影响的表征

• 批准号: 9483714
• 负责人: Brandon Jarrod Henderson
• 金额: $ 21.67万
• 依托单位: MARSHALL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9483714
• 关键词: Address; Animals; Basic Science; Behavior; Behavioral Assay; Binding; Binding Sites; Biological Assay; Biophysics; Brain; Cessation of life; Charge; Chronic; Cigar; Cigarette; Collaborations; Complement; Data; Doctor of Philosophy; Dopamine; Dose; Drug usage; Electrophysiology (science); Event; Exhibits; Exposure to; Faculty; Fluorescence Resonance Energy Transfer; Genetic; Goals; Investigation; Learning; Legal; Medical; Memory; Menthol; Mentors; Methods; Microscopy; Midbrain structure; Molecular Biology; Mus; National Institute of Drug Abuse; Neurobiology; Neurons; Neuropharmacology; Neurosciences; Nicotine; Nicotine Dependence; Nicotinic Receptors; Oral Tobacco; Pathway interactions; Periodicity; Pharmacology; Phase; Play; Population; Positioning Attribute; Prevalence; Property; Public Health; Rattus; Reporting; Research; Research Personnel; Resources; Rewards; Rodent; Role; Running; Safety; Saline; Scanning; Science; Self Administration; Slice; Smoke; Smoker; Smoking Behavior; Supervision; Techniques; Tobacco; Tobacco Dependence; Training; United States; Up-Regulation; addiction; cell type; cigarette smoking; computational chemistry; cost; dopaminergic neuron; drug of abuse; gamma-Aminobutyric Acid; improved; in vivo; interest; nicotinic receptor beta2; novel; post-doctoral training; preference; premature; public health relevance; receptor upregulation; response; skills; smoking cessation; stoichiometry; tool; translational impact

 DESCRIPTION (provided by applicant): Currently, it is unknown how menthol may play a role in the addiction to nicotine. Despite this, it is clear that people who smoke menthol cigarettes exhibit poorer quit rates compared to those who smoke non- menthol cigarettes. I have a unique opportunity at Caltech to gain understanding of menthol's effects as I have access to unique tools that will facilitate the in vivo characterization of menthol's effect on the addiction to nicotine. I plan to combine multiple in vivo techniques to look specifically at how menthol alters nicotine reward, dopamine release, and neurobiology. These include: 1) behavioral assays with conditioned place preference and self-administration; 2) in vivo and ex vivo voltammetry assays; 3) electrophysiology using mouse brain slices; and 4) microscopy to study changes in neurobiology. I, along with NIDA, hold a strong interest in menthol and how menthol plays a role in nicotine addiction. I have preliminary data showing that menthol enhances nicotine reward-related behavior in mice in a conditioned place preference assay. Despite this, there is much that we need to know concerning menthol. This proposal aims to address many of the concerns issued recently by NIDA concerning menthol. The assays (behavior, voltammetry, microscopy, and electrophysiology) are planned to be synergistic. Doses of nicotine and menthol found to be efficacious in behavior assays will be used in both microscopy and electrophysiology assays. Through these proposed assays, my goal is to collect data that will further the aims of NIDA by providing the basic research that will improve public health and encourage new science that will reduce tobacco dependence. To accomplish this proposed research plan, I will pursue two years of additional postdoctoral training in animal behavioral assays and fast scan cyclic voltammetry under the supervision and direction of my mentors. Henry Lester, PhD (Caltech), my primary mentor is an expert in neuroscience, neurobiology, and biophysics. Marina Picciotto, PhD (Yale) and Nii Addy, PhD (Yale) are both experts in neuropharmacology, rodent behavior, rodent genetics, and mechanisms in reward, learning, and memory. At Caltech and Yale, I will have all the necessary guidance, tools, and resources to be adequately trained in the new assays and successfully complete this project. With the skills attained from my additional training, I will transition to an academic faculty position as a independent investigator.

 描述(申请人提供)：目前，薄荷醇如何在尼古丁成瘾中发挥作用尚不清楚。尽管如此，很明显，吸烟薄荷醇香烟的人比那些抽非薄荷醇香烟的人戒烟率更低。在加州理工学院，我有一个独特的机会来了解薄荷醇的影响，因为我可以获得独特的工具，这些工具将有助于在体内表征薄荷醇对尼古丁成瘾的影响。我计划结合多种体内技术，专门研究薄荷醇如何改变尼古丁奖赏、多巴胺释放和神经生物学。这些方法包括：1)条件性位置偏爱和自我给药的行为分析；2)体内和体外伏安分析；3)使用小鼠脑片进行电生理学；以及4)显微镜研究神经生物学的变化。我和NIDA对薄荷醇以及薄荷醇如何在尼古丁成瘾中发挥作用抱有浓厚的兴趣。我有初步数据表明，在条件性位置偏爱试验中，薄荷醇增强了小鼠的尼古丁奖赏相关行为。尽管如此，关于薄荷醇，我们还有很多需要知道的。这项提案旨在解决NIDA最近提出的许多关于薄荷醇的问题。这些分析(行为、伏安法、显微镜和电生理学)计划是协同的。在行为测试中被发现有效的尼古丁和薄荷脑剂量将被用于显微镜和电生理测试。通过这些建议的化验，我的目标是收集数据，通过提供改善公众健康和鼓励减少烟草依赖的新科学的基础研究，促进NIDA的目标。为了完成这项拟议的研究计划，我将在导师的监督和指导下，在动物行为分析和快速扫描循环伏安法方面进行两年的额外博士后培训。亨利·莱斯特博士(加州理工学院)，我的主要导师是神经科学、神经生物学和生物物理学方面的专家。Marina Picciotto博士(耶鲁大学)和Nii Addy博士(耶鲁大学)都是神经药理学、啮齿动物行为、啮齿动物遗传学以及奖赏、学习和记忆机制方面的专家。在加州理工学院和耶鲁大学，我将拥有所有必要的指导、工具和资源，以便在新的测试中得到充分的培训，并成功完成这个项目。凭借我从额外培训中获得的技能，我将过渡到一个学术教职，成为一名独立调查员。