Ethanol Drinking in Rats: Accumbal Circuit Activity

描述(由申请人提供)： 候选人：多尼塔·L·罗宾逊，博士，北卡罗来纳大学医学院精神病学系和酒精研究中心助理教授。她接受的培训是分析化学方法学，用于在自由活动的动物中测量大脑中的多巴胺和乙醇。她的直接目标有两个：(1)学习行为动物的多神经元电生理记录；(2)学习一种技术，在行为动物的同一微驻极体上测量神经元放电和亚秒多巴胺信号。她的长期目标是在独立的校外拨款的资助下，在乙醇神经药理学和行为学方面开发一个高质量的独立研究计划。这一研究事业奖将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，帮助罗宾逊博士实现这些目标。环境：北卡罗来纳大学提供实验室空间、设备以及与教职员工接触的通道，这将使罗宾逊博士能够完成本文提出的培训和研究。联合电生理学电化学技术是由Regina Carelli博士和Mark Wightman博士开发的，因此他们最有资格赞助这项申请。北卡罗来纳大学酒精研究中心有许多著名的乙醇专家 药理学和自我给药行为，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北卡罗来纳大学成功地开展独立研究项目。研究：伏隔核(NA)是一个边缘-运动集成器，吸收记忆和驱动输入，并协调反应行为输出。解剖学和药理学证据表明，NA的核心和外壳亚区在动机行为中扮演着重叠但不同的角色。拟议的实验将检查大鼠饮酒行为中NA的核心和外壳功能，特别关注多巴胺输入如何在毫秒级时间尺度上调节NA活动。将使用多电极阵列(具体目标1和2)来充分表征在对同时的乙醇和水的操作响应期间，NA核心和外壳中的神经元的模式。在同时对乙醇和水进行操作响应期间，将评估NA核心和外壳中的时相(亚秒)多巴胺活性，同时记录附近NA神经元的放电模式(特定目标3和4)。最后，在手术前，将使用纳曲酮对NA细胞放电模式(特定目标2)和相性多巴胺信号(特定目标4)的阿片调制进行评估。总之，这些实验将为NA在行为过程中的生理、药理学和化学相互作用提供新的有价值的信息，将乙醇与水强化和核心与外壳进行比较。这些研究将以一种独特和创新的方法最好地训练候选人，并显著促进我们对酒精饮酒的神经控制的理解。

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.