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Behavioral Neuroscience Program
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Regina M. Carelli, Ph.D. Director of Behavioral Neuroscience Program
Last updated: 06/03/2008 Why are drugs of abuse such as cocaine so addictive? How can cues associated with prior drug use in human addicts (e.g., drug paraphernalia) elicit such powerful drug craving following months or even years of drug abstinence? Moreover, is it true that addictive compounds like cocaine "hijack" the parts of the brain that evolved to recognize and consume 'natural' rewards like food and water? These are some of the questions that drive my research program at UNC. My primary research interests are to understand how the brain processes information about natural (nondrug) rewards, and how drugs of abuse such as cocaine alter this system and lead to addiction. Numerous investigations have demonstrated that the rewarding properties of abused substances such as cocaine and ‘natural’ reinforcers such as food and water are mediated by the brain’s ‘reward system’, which includes the nucleus accumbens and its dopaminergic input. Ongoing investigations in my laboratory employ a number of techniques to elucidate how this brain region contributes to reward-related behaviors. Electrophysiological methods involve the use of microwire electrode arrays to monitor neural activity (cellular action potentials) in the nucleus accumbens while animals perform a behavioral task. An electrochemical technique (fast-scan cyclic voltammetry) is also used to detect dopamine release in the nucleus accumbens with unprecedented temporal precision. Finally, these techniques are combined to record both dopamine concentration and cellular activity within the same microenvironment. Using these approaches, our work provides information on the dynamic properties of dopamine release in awake animals, how this signaling may modulate the activation of specific neurons in the accumbens during goal-directed behaviors, and ultimately how drugs of abuse such as cocaine modify this system and result in drug addiction.
Extracellular waveform of nucleus accumbens neuron recorded from an awake and behaving animal
Subsecond dopamine release detected using in vivo fast-scan cyclic voltammetry Undergraduate
Psychology 222 (Learning) Graduate Psychology 702 (Behavior and Its Biological Basis II) Psychology 720/721 (Research Seminar in Experimental Psychology) Owesson-White CA, Cheer JF, Beyene M, Carelli RM, Wightman RM (in press) Dynamic changes in accumbens dopamine linked to learning of intra-cranial self-stimulation. Proceedings of the National Academy of Sciences. Wheeler RA, Twining RC, Jones JJ, Slater JM, Grigson PS, Carelli RM (2008) Behavioral and electrophysiological indices of negative affect predict cocaine self-administration, Neuron, 57, 774–785. Day JJ,.Roitman MF, Wightman RM, Carelli RM (2007) Associative learning mediates dynamic shifts in dopamine signaling within the nucleus accumbens. Nature Neuroscience, 10(8): 1020-1028 . Cheer JF, Aragona BJ, Heien MLAV, Seipel AT, Carelli RM, Wightman RM (2007) Coordinated accumbal dopamine release and neural activity drive goal-directed behavior. Neuron, 54(2):237-244. Hollander JA, Carelli RM (2007) Cocaine-associated stimuli increase cocaine-seeking and activate accumbens core neurons following abstinence. The Journal of Neuroscience, 27(13):3535-3539.
Day JJ, Carelli RM (2007). The Nucleus Accumbens and Pavlovian Reward Learning. Invited review for The Neuroscientist 13(2):148-159. Aragona BJ, Carelli RM (2006) Dynamic Neuroplasticity and the Automation of Motivated Behavior. Learning and Memory, 13(5):558-559. Wheeler, R.A., & Carelli, R.M. (2006). The neuroscience of pleasure: Focus on Ventral pallidum firing codes hedonic reward: when a bad taste turns good. Journal of Neurophysiology, 96(5):2175-2176. Day, J.J., Wheeler, R.A., Roitman, M.F., & Carelli, R.M. (2006). Nucleus accumbens neurons encode Pavlovian approach behaviors: evidence from an autoshaping paradigm. The European Journal of Neuroscience, 23(5):1341-51. pdf online The definitive version is available at www.blackwell-synergy.com. Cheer, J.F., Heien, M.L., Garris, P.A., Carelli, R.M., & Wightman, R.M. (2006). Simultaneous dopamine and single-unit recordings reveal accumbens GABAergic responses: implications for intracranial self-stimulation. Proceedings of the National Academy of Sciences, 102(52):19150-5. online Stuber, G.D., Wightman, R.M., & Carelli, R.M. (2005). Extinction of cocaine self-administration reveals functionally and temporally distinct dopaminergic signals in the nucleus accumbens. Neuron, 46(4):661-9. online Hollander, J.A. & Carelli, R.M. (2005).
Abstinence from cocaine self-administration heightens neural encoding of goal-directed behaviors in the accumbens. Roitman, M.F., Wheeler, R.A., & Carelli, R.M. (2005). Nucleus accumbens neurons are innately tuned for rewarding and aversive taste stimuli, encode their predictors, and are linked to motor output. Neuron, 45(4):587-97. online Carelli, R.M. & Wightman, R.M. (2004). Functional microcircuitry in the accumbens underlying drug addiction: insights from real-time signaling during behavior. Current Opinion in Neurobiology, 14(6):763-8. Roitman,
M.R., Phillips, P.E.M., Stuber, G., Wightman, R.M., & Carelli, R.M. (2004). Dopamine operates as
a subsecond modulator of food seeking. The
Journal of Neuroscience, 24(6): 1265-1271. Carelli, R.M., & Wondolowski, J. (2003). Selective encoding of cocaine versus natural rewards by nucleus accumbens neurons is not related to chronic drug exposure. The Journal of Neuroscience, 23: 11214-11223. pdf online © Society for Neuroscience Carelli, R.M., Williams, J.G., & Hollander, J. (2003).
Basolateral amygdala neurons encode
cocaine self-administration and cocaine-associated cues. The Journal of Neuroscience, 23: 8204-8211. Phillips, P.E.M.,
Stuber, G.D., Heien M.L.A.V., Wightman, R.M., & Carelli, R.M. (2003). Subsecond
dopamine triggers cocaine seeking, Nature,
422(6932):614-618.
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Regina M. Carelli, Ph.D. Behavioral Neuroscience Program Department of Psychology |
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