Ethanol Drinking in Rats: Accumbal Circuit Activity

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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.