THE ROLE OF RAPID DOPAMINE SIGNALING WITHIN THE NUCLEUS ACCUMBENS IN NATURAL AND DRUG REWARD-SEEKING BEHAVIORS Public Deposited

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  • March 19, 2019
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  • Cameron, Courtney
    • Affiliation: College of Arts and Sciences, Department of Psychology and Neuroscience
Abstract
  • Learning about rewards and appropriately directing behaviors to obtain them is critical for survival. These processes are subserved by a distributed network of brain nuclei including the nucleus accumbens (NAc) and its dopaminergic input. In vivo electrophysiology studies have repeatedly provided evidence that NAc neurons encode goal-directed behaviors for both natural and drug rewards. Specifically, work from this laboratory has shown that subsets of NAc neurons exhibit largely differential, nonoverlapping firing patterns during operant responding for natural rewards (food, water, or sucrose) versus intravenous cocaine (Carelli et al., 2000; Carelli, 2002; Carelli & Wondolowski, 2003; Carelli & Wondolowski, 2006; Cameron & Carelli, 2012). Furthermore, the percentage of NAc neurons that encode goal-directed behaviors for cocaine is dramatically increased following 30 days of cocaine abstinence (Hollander & Carelli, 2005; Hollander & Carelli, 2007). While we have observed rapid dopamine (DA) signaling in the NAc during responding for natural (Roitman et al, 2004) and drug (Phillips et al., 2003) rewards on a timescale similar to NAc phasic cell firing, it is not known whether this DA signaling acts in a manner analogous to NAc phasic activity. The first set of experiments detailed in this dissertation used electrochemical recording techniques to measure rapid DA release in the NAc core during performance of two different tasks: a sucrose/cocaine or sucrose/food multiple schedule. This design allowed us to compare DA release dynamics in specific locations in the NAc during operant responding for two natural rewards, versus a natural reward and intravenous cocaine. These experiments revealed that, unlike our prior electrophysiology work, rapid DA release in the NAc was not reinforcer specific during performance of a sucrose/cocaine multiple schedule. In the second set of experiments, we used the same data set obtained from Aim 1 to compare basic shifts in pH in discrete locations in the NAc core and determine if aspects of this signaling differed during each phase of the sucrose/cocaine multiple schedule. Our findings revealed that although increases in pH were observed under both reinforcer conditions, the dynamics of this signaling were significantly different when animals responded for intravenous cocaine versus the natural reward, sucrose. The final set of experiments examined the effects of one month of cocaine abstinence on DA release and uptake dynamics in the NAc core. We found that a month of cocaine abstinence potentiated the peak concentration of electrically evoked DA in the NAc following an acute injection of cocaine. Taken together, the results of these studies indicate that DA signaling in the NAc is highly dynamic and can be influenced by many factors, including the type of reinforcer (natural or drug) being self-administered or the pattern of drug exposure (1 day versus 30 days of abstinence). Furthermore, rapid DA signaling does not interact with NAc cell firing in a simple manner, but instead differentially modulates neuronal activity depending on many factors including reward type, specific afferent-efferent projections, and ongoing behavior.
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  • In Copyright
Advisor
  • Wightman, R. Mark
  • Hollins, Mark
  • Thiele, Todd
  • Carelli, Regina
  • Stuber, Garret
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2014
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  • Chapel Hill, NC
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