ETHANOL EFFECTS ON NICOTINIC ACETYLCHOLINE RECEPTORS

该提案是K01指导科学家发展奖的申请。候选人马克·W·诺瓦克博士是南卡罗来纳医科大学药物和酒精项目中心(CDAP)的助理教授。K01奖将允许候选人将他在烟碱型乙酰胆碱受体(NAChRs)研究方面的现有研究技能与酒精研究领域相结合。虽然候选人在nAChRs研究方面有研究经验，但他之前在酒精领域没有研究经验。拟议的培训计划旨在通过教学工作、专门针对乙醇研究的电生理学和组织培养技术的培训，以及使用涉及体内酒精暴露的动物模型的“动手”培训，为应聘者提供与酒精相关的广泛研究知识。在CDAP内部，有酒精领域的资深研究人员，从而确保成功完成培训目标。此外，下面描述的拟议研究项目补充了这些培训目标，并解决了候选人在开发专注于尼古丁-乙醇相互作用的独立研究计划方面的研究兴趣。考虑到酒精和烟草产品的共同使用，了解乙醇和尼古丁的相互作用是一个相关的健康问题。虽然这些物质联合使用的原因还不是很清楚，但越来越多的证据表明，乙醇和尼古丁的相互作用参与了中枢神经系统。乙醇和尼古丁已被证明会影响大脑中的各种神经化学系统。中枢神经系统尼古丁的主要靶点是神经元的nAChRs。有理由认为，神经元nAChRs可能部分参与了中枢乙醇/尼古丁的相互作用。然而，尽管乙醇对其他配体门控离子通道(NMDA、GABAA和5-HT3受体)的影响已经引起了人们的关注，但乙醇对神经元nAChR功能的影响还没有得到广泛的研究。为了解决这个研究问题，拟议的研究将检查急性和慢性乙醇暴露对神经元nAChR功能的影响。电生理全细胞膜片钳技术将用于评估原代培养大鼠海马神经元的nAChR功能。拟议中的研究结果将有助于了解乙醇和尼古丁对大脑功能的影响这一长期目标。总体而言，K01奖项将使诺瓦克博士能够将他的实验技能扩展到酒精研究领域，并实现他的目标，即开发一个研究酒精和尼古丁相互作用的独立研究项目。

This proposal is a K01 Mentored Scientist Development Award Application. The candidate, Dr. Mark W. Nowak, is an Assistant Professor in the Center for Drug and Alcohol Programs (CDAP) at the Medical University of South Carolina. A K01 award would allow the candidate to integrate his existing research skills in the study of nicotinic acetylcholine receptors (nAChRs) with the field of alcohol research. While the candidate has research experience in the study of nAChRs, he has no prior research experience in the alcohol field. The proposed training plan is designed to provide the candidate with a broad knowledge of alcohol-related research through didactic work, training in electrophysiological and tissue culture techniques specific to ethanol research, and "hands-on" training in the use of animal models involving in vivo ethanol exposure. Within CDAP, there are established researchers in the alcohol field, thus ensuring the successful completion of the training objectives. Further, the proposed research project described below complements these training objectives and addresses the candidate's research interests in developing an independent research program focused on nicotine-ethanol interactions. Understanding ethanol-nicotine interactions is a relevant health issue given the well-documented comorbid use of alcohol and tobacco products. While the reasons for the combined use of these substances are not well-understood, there is a growing body of evidence suggesting involvement of ethanol-nicotine interactions in the CNS. Ethanol and nicotine have been shown to affect a wide variety of neurochemical systems in the brain. The main CNS target for nicotine are the neuronal nAChRs. It is reasonable to suggest that neuronal nAChRs may, in part, be involved in central ethanol/nicotine interactions. Nevertheless, while the effects of ethanol on other ligand-gated ion channels (NMDA, GABAA and 5-HT3 receptors) have received considerable attention, the effects of ethanol on neuronal nAChR function have not been extensively studied. To address this research question, the proposed research studies will examine the effects of acute and chronic ethanol exposure on neuronal nAChR function. Electrophysiological whole-cell patch clamp techniques will be utilized to assess neuronal nAChR function in primary rat hippocampal neuronal cultures. The findings from the proposed studies will contribute to the long-term goal of understanding the effects of ethanol and nicotine on brain function. Overall, this K01 award would allow Dr. Nowak to expand his experimental skills into the field of alcohol research as well as achieve his goal of developing an independent research program studying alcohol-nicotine interactions.