ETHANOL EFFECTS ON NICOTINIC ACETYLCHOLINE RECEPTORS

该提案是K01指导科学家发展奖申请。候选人Mark W. Nowak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乙酰胆碱受体（nachr）研究中的现有研究技能与酒精研究领域相结合。虽然候选人在nachr研究方面有研究经验，但他之前没有酒精领域的研究经验。拟议的培训计划旨在通过教学工作、针对乙醇研究的电生理和组织培养技术培训，以及使用涉及体内乙醇暴露的动物模型的“动手”培训，为候选人提供与酒精相关的广泛研究知识。在CDAP内部，有成熟的酒精领域的研究人员，从而确保了培训目标的顺利完成。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一个专注于尼古丁-乙醇相互作用的独立研究项目方面的研究兴趣。考虑到酒精和烟草产品的合并症，了解乙醇-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尚不清楚，但越来越多的证据表明乙醇-尼古丁在中枢神经系统中的相互作用。酒精和尼古丁已经被证明会影响大脑中各种各样的神经化学系统。尼古丁在中枢神经系统的主要作用靶点是神经元nachr。我们有理由认为神经元nachr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）的影响已受到相当多的关注，但乙醇对神经元nAChR功能的影响尚未得到广泛研究。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被用于评估大鼠海马神经元培养中神经元nAChR的功能。拟议研究的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。总的来说，这个K01奖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，并实现他开发一个研究酒精-尼古丁相互作用的独立研究项目的目标。

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.