Ethanol Drinking in Rats: Accumbal Circuit Activity

描述（由申请人提供）： 候选人：Donita L.罗宾逊博士，是北卡罗来纳州医学院精神病学系和酒精研究中心的助理教授。她的训练一直是在自由移动的动物的多巴胺和乙醇的大脑测量分析化学方法。她的近期目标是双重的：（1）学习行为动物的多神经元电生理记录和（2）学习在行为动物的同一微电极上测量神经元放电和亚秒多巴胺信号的技术。她的长期目标是开发一个高质量的，独立的乙醇神经药理学和行为研究计划，由独立的校外赠款资助。这项研究职业奖将帮助罗宾逊博士通过提供上述方法的扎实培训以及将这些技术应用于乙醇研究的研究支持来实现这些目标。工作环境：北卡罗来纳州大学提供实验室空间、设备以及教职员工，使罗宾逊博士能够完成本文提出的培训和研究。组合电生理学电化学技术由Regina Carelli和Mark Wightman博士开发，因此他们最有资格申办本申请。酒精研究中心有许多著名的乙醇专家 药理学和自我管理行为，包括克莱德霍奇博士。赞助部门和机构致力于并支持罗宾逊博士在斯坦福大学成功发展独立的研究项目。研究：延髓核（NA）是一个边缘运动整合器，吸收记忆和驱动输入，协调反应性行为输出。解剖学和药理学证据表明，核心和壳亚区的NA执行重叠，但不同的动机行为的作用。拟议的实验将检查NA核心和外壳的功能，在大鼠的乙醇饮酒行为，特别关注多巴胺输入如何调节NA活动的毫秒时间尺度。将使用多电极阵列（具体目标1和2）充分表征在对并发乙醇和水的操作性响应期间发现NA核和壳中的神经元模式。在对同时发生的乙醇和水的操作性响应期间，将在NA核和壳中评价相（亚秒）多巴胺活性，同时记录附近NA神经元的放电模式（特定目的3和4）。最后，将在操作期前用纳洛酮给药评估NA细胞放电模式（特定目标2）和阶段性多巴胺信号（特定目标4）的阿片调节。总之，这些实验将提供新的和有价值的信息的相互作用的生理学，药理学和化学的NA在行为过程中，比较乙醇水增强和核壳。这些研究将以独特和创新的方法最好地训练候选人，并显着推进我们对乙醇饮用神经控制的理解。

DESCRIPTION (provided by applicant): Candidate: Donita L. Robinson, Ph.D., is an Assistant Professor in the Department of Psychiatry and the Center for Alcohol Studies at the University of North Carolina School of Medicine. Her training has been in analytical chemical methodology for brain measurements of dopamine and ethanol in freely-moving animals. Her immediate goal is twofold: (1) to learn multineuron electrophysiological recording in behaving animals and (2) to learn a technique to measure neuronal firing and subsecond dopamine signaling at the same microelectrede in behaving animals. Her long-term goal is to develop a high-quality, independent research program in ethanol neuropharmacology and behavior, funded by independent extramural grants. This Research Career Award will help Dr. Robinson accomplish these goals by providing solid training in the above methods as well as research support to apply these techniques to ethanol studies. Environment: The University of North Carolina provides laboratory space, equipment, and access to faculty and staff that will allow Dr. Robinson to accomplish the training and research proposed herein. The combined electrophysiology electrochemistry technique was developed by Drs. Regina Carelli and Mark Wightman, who are thus best qualified to sponsor this application. The UNC Center for Alcohol Studies contains many well known experts in ethanol pharmacology and self-administration behavior, including Dr. Clyde Hodge. The sponsoring departments and institution are committed and supportive of Dr. Robinson's development of a successful, independent research program at UNC. Research: The nucleus accumbens (NA) is a limbic-motor integrator, assimilating memory and drive input and coordinating responsive behavioral output. Anatomical and pharmacological evidence indicates that the core and shell subregions of the NA perform overlapping but distinct roles in motivated behavior. The proposed experiments will examine NA core and shell functions in ethanol drinking behavior in rats, with particular focus on how dopamine input modulates NA activity on the millisecond timescale. Finding patterns of neurons in the NA core and shell during operant responding for concurrent ethanol and water will be fully characterized using multi-electrode arrays (Specific Aims 1 and 2). Phasic (subsecond) dopamine activity will be evaluated in the NA core and shell during operant responding for concurrent ethanol and water, while simultaneously recording firing patterns of nearby NA neurons (Specific Aims 3 and 4). Finally, opiate modulation of NA cell firing patterns (Specific Aim 2) and phasic dopamine signals (Specific Aim 4) will be assessed with naltrexone administration before the operant session. Together, these experiments will provide new and valuable information on the interaction of physiology, pharmacology and chemistry in the NA during behavior, comparing ethanol to water reinforcement and core to shell. These studies will best train the candidate in a unique and innovative method, and significantly advance our understanding of neural control of ethanol drinking.