Numerous investigations indicate that the nucleus accumbens (Acb) is crucially involved in mediating the reinforcing actions of drugs of abuse such as cocaine and `natural' reinforcers such as food and water. We recently completed a series of studies that examined the activity of the same Acb neurons in rats responding on multiple schedules for either two distinct `natural' reinforcers (water and food), or one of those `natural' reinforcers and the intravenous self-administration of cocaine (Carelli et al., 2000; Appendix D). The results showed that the majority of neurons tested exhibited similar, overlapping neuronal firing patterns across the two `natural' reinforcer conditions. In contrast, the majority of neurons examined (> 90%) exhibited differential, nonoverlapping firing patterns relative to operant responding for water (or food) vs. cocaine reinforcement. Given these findings, four experiments are proposed in this application to provide critical information regarding factors that influence and/or control Acb reinforcement-related cell firing in behaving animals. Exp. 1 will determine the anatomic distribution of neurons in the Acb that selectively encode information related to water vs. cocaine reinforcement. This will be accomplished by the strategic positioning of microelectrodes into the core, shell and/or rostral pole of the Acb, and the specific `marking' of wires from which reinforcer selective cell firing was recorded during a water/cocaine multiple schedule. Exp. 2 will extend that study and determine if reinforcer selective cell firing is apparent during initial exposure to cocaine or if it is a direct consequence of repeated self-administration experience. Information gained in those studies will be expanded in Exps. 3 & 4 by determining the effects of interruption of drug access (abstinence) on cocaine selective cell firing. This is a critical issue since cocaine addiction in humans is typically characterized by periods of abstinence from drug taking and relapse (Gawin, 1991; O'Brien et al., 1992). Specifically, Exp. 3 will determine the firing properties of Acb neurons following various periods of cocaine abstinence (2, 4 and 8 weeks). Exp. 4 will determine the effects of cocaine abstinence on the associative properties of Acb cell firing documented in a number of published reports by the PI. Results of Exp. 4 will be directly relevant to understanding the biological basis of stimulus control in cocaine addiction reported to be a major contributor to problems in human drug abusers (O'Brien et al., 1992; Childress et al., 1999). Collectively, these studies will provide important insight into the functional organization of the Acb and its role in reinforcement-related processing in behaving animals.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA014339-03
Application #
6619527
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Volman, Susan
Project Start
2001-07-01
Project End
2006-10-31
Budget Start
2003-06-15
Budget End
2004-05-31
Support Year
3
Fiscal Year
2003
Total Cost
$252,612
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Haake, Rachel M; West, Elizabeth A; Wang, Xuefei et al. (2018) Drug-induced dysphoria is enhanced following prolonged cocaine abstinence and dynamically tracked by nucleus accumbens neurons. Addict Biol :
Moschak, Travis M; Wang, Xuefei; Carelli, Regina M (2018) A Neuronal Ensemble in the Rostral Agranular Insula Tracks Cocaine-Induced Devaluation of Natural Reward and Predicts Cocaine Seeking. J Neurosci 38:8463-8472
Moschak, Travis M; Terry, Douglas R; Daughters, Stacey B et al. (2018) Low distress tolerance predicts heightened drug seeking and taking after extended abstinence from cocaine self-administration. Addict Biol 23:130-141
Hurley, Seth W; West, Elizabeth A; Carelli, Regina M (2017) Opposing Roles of Rapid Dopamine Signaling Across the Rostral-Caudal Axis of the Nucleus Accumbens Shell in Drug-Induced Negative Affect. Biol Psychiatry 82:839-846
Cameron, Courtney M; Wightman, R Mark; Carelli, Regina M (2016) One month of cocaine abstinence potentiates rapid dopamine signaling in the nucleus accumbens core. Neuropharmacology 111:223-230
Green, Jennifer L; Dykstra, Linda A; Carelli, Regina M (2015) Examination of cocaine dose in a preclinical model of natural reward devaluation by cocaine. Behav Pharmacol 26:398-402
Carelli, Regina M; West, Elizabeth A (2014) When a good taste turns bad: Neural mechanisms underlying the emergence of negative affect and associated natural reward devaluation by cocaine. Neuropharmacology 76 Pt B:360-9
Cerri, Domenic H; Saddoris, Michael P; Carelli, Regina M (2014) Nucleus accumbens core neurons encode value-independent associations necessary for sensory preconditioning. Behav Neurosci 128:567-578
Saddoris, Michael P; Carelli, Regina M (2014) Cocaine self-administration abolishes associative neural encoding in the nucleus accumbens necessary for higher-order learning. Biol Psychiatry 75:156-64
Sugam, Jonathan A; Saddoris, Michael P; Carelli, Regina M (2014) Nucleus accumbens neurons track behavioral preferences and reward outcomes during risky decision making. Biol Psychiatry 75:807-816

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