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

 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。尽管如此，很明显，与吸非薄荷醇香烟的人相比，吸薄荷醇香烟的人表现出更差的戒烟率。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作用的体内表征。我计划将联合收割机多种体内技术结合起来，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。其中包括：1）具有条件位置偏好和自我施用的行为测定; 2）体内和离体伏安法测定; 3）使用小鼠脑切片的电生理学;和4）研究神经生物学变化的显微镜。 我，沿着NIDA，对薄荷醇以及薄荷醇如何在尼古丁成瘾中发挥作用持有浓厚的兴趣。我有初步的数据表明，薄荷醇增强了条件位置偏爱实验中小鼠的尼古丁奖励相关行为。尽管如此，关于薄荷醇我们需要知道的还有很多。该提案旨在解决NIDA最近对薄荷醇的许多担忧。 试验（行为、伏安法、显微镜和电生理学）计划具有协同作用。在行为试验中发现有效的尼古丁和薄荷醇剂量将用于显微镜检查和电生理学试验。通过这些拟议的分析，我的目标是收集数据，通过提供基础研究来促进NIDA的目标，这些基础研究将改善公共健康，并鼓励减少烟草依赖的新科学。 为了完成这个拟议的研究计划，我将在导师的监督和指导下，继续进行为期两年的动物行为测定和快速扫描循环伏安法的博士后培训。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励，学习和记忆机制的专家。在加州理工学院和耶鲁大学，我将获得所有必要的指导、工具和资源，以便在新的分析方面得到充分的培训，并成功完成这个项目。随着我从额外的培训获得的技能，我将过渡到一个学术教师的位置作为一个独立的调查员。

 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.