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

薄荷醇对尼古丁强化和烟碱受体神经生物学影响的表征

基本信息

批准号：
9109981
负责人：
Brandon Jarrod Henderson
金额：
$ 15.12万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-03-01 至 2017-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9109981
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 Drosophila acetylcholine receptor alpha-subunit Electrophysiology (science)Event Exhibits Exposure to Faculty Flavoring 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 Pharmacology Phase Play Population Positioning Attribute Prevalence Property Psychological reinforcement 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 computational chemistry cost dopaminergic neuron drug of abuse gamma-Aminobutyric Acid improved in vivo interest nicotinic receptor beta2 non-smoker non-smoking novel post-doctoral training preference premature public health relevance response skills smoking cessation stoichiometry tool

项目摘要

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（由申请人提供）：目前尚不清楚薄荷醇如何在尼古丁成瘾中发挥作用，但很明显，与吸非薄荷醇香烟的人相比，吸薄荷醇香烟的人的戒烟率较低。我在加州理工学院有一个独特的机会来了解薄荷醇的作用，因为我可以使用独特的工具来促进薄荷醇对尼古丁成瘾的体内表征。计划结合多种体内技术来具体研究薄荷醇如何改变尼古丁奖励、多巴胺释放和神经生物学，其中包括：1）条件性位置偏好和自我给药的行为测定；2）体内和离体伏安法测定； ) 使用小鼠脑切片进行电生理学；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的作用抱有浓厚的兴趣。我的初步数据表明，在条件性位置偏好实验中，薄荷醇可以增强小鼠的尼古丁奖励相关行为，尽管如此，我们仍然需要了解很多有关薄荷醇的信息。 NIDA 最近发布了有关薄荷醇的担忧，计划进行的检测（行为、伏安法、显微镜和电生理学）发现尼古丁和薄荷醇的剂量具有协同作用。在行为分析中有效将用于显微镜和电生理学分析，通过这些拟议的分析，我的目标是收集数据，通过提供改善公共卫生和鼓励新科学的基础研究来进一步实现 NIDA 的目标。为了完成这项拟议的研究计划，我将在导师亨利·莱斯特博士（加州理工学院）的监督和指导下进行两年的动物行为测定和快速扫描循环伏安法的额外博士后培训。我的主要导师是神经科学、神经生物学和生物物理学专家 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励、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，以便在新的检测中接受充分的培训，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。作为独立研究者的学术教职。