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. The PI completed a series of electrophysiological studies that examined the activity of the same Acb neurons in rats responding on multiple schedules for either two 'natural' reinforcers (water and food), or one of those 'natural' reinforcers and the intravenous self-administration of cocaine (Carelli et al., 2000). 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) versus cocaine reinforcement. Those findings provide important insight into the functional microcircuitry in the Acb that underlies reward processing and goal-directed behavior (Carelli and Wightman, 2004). Here, four specific aims are proposed to expand those findings and examine complex interactions between cellular discharges and behavior related to cocaine versus 'natural' rewards. Since natural rewards are typically devalued in cocaine addicts in comparison with drugs of abuse, Exp. 1 will determine if alterations in Acb cell firing occur during presentation of a natural reward that predicts access to cocaine. In the last funding period, the PI reported dynamic increases in the percentage of Acb neurons that encode cocaine-directed behaviors following interruption of cocaine access (abstinence). Exp. 2 will determine if those findings are generalizable to natural rewards by determining the effects of interruption of access to sucrose on Acb cell firing characteristics during sucrose-directed behavior. Exp. 3 will expand our abstinence studies and determine if separate neural circuits in the Acb encoding cocaine versus natural reward remain evident following interruption of cocaine access. Exp. 4 will determine if medial prefrontal cortical (mPFC) neurons are responsive to cocaine-associated stimuli before versus following cocaine abstinence, a phenomenon well-documented for Acb cells in a number of reports by the PI. The results are directly relevant to understanding the biological basis of stimulus control in human cocaine addiction in which stimuli previously associated with drug taking are strong elicitors of 'craving' and often lead to relapse following periods of drug abstinence (O'Brien et al., 1992; Childress et al., 1999). ? ? ?

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IFCN-A (07))
Program Officer
Volman, Susan
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Chapel Hill
Schools of Arts and Sciences
Chapel Hill
United States
Zip Code
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

Showing the most recent 10 out of 38 publications