The nucleus accumbens has long been implicated as an essential brain region for the manifestation of reward-related behaviors and addiction. Furthermore, it is known that a primary chemical component of 'reward' in the nucleus accumbens comes from dopaminergic input from the ventral tegmental area. Evidence from electrophysiological studies suggests that dopaminergic burst firing (occurring over seconds) may be an important mediator of associative learning between environmental cues and the primary effects of a reinforcer. While previous microdialysis and electrochemical studies have investigated how dopamine levels can change over minutes to hours during cocaine self administration, little is known about how dopamine changes on a second to second timescale. The proposed experiments plan to examine the role of phasic dopamine neurotransmission in the nucleus accumbens during cocaine self-administration in rats. In Experiment 1, we will determine whether differences exist between the two key subregions of the nucleus accumbens (the core and shell) with respect to phasic dopamine during cocaine self-administration. In preliminary experiments transient increases in dopamine were seen immediately after the lever-press for cocaine in the core of the NAc The second proposed experiment will examine how extinction/reinstatement of cocaine self-administration behavior affects phasic dopamine release in the nucleus accumbens. During extinction each lever-press will no longer result in cocaine delivery, and any changes in phasic dopamine will be examined. In reinstatement, cocaine infusions will again be paired with both drug associated cues and lever presses, and we will examine if this subsequent pairing of reinforcer with drug-associated cues alters phasic dopamine. These studies will further the understanding of how dopaminergic signaling is involved in drug reinforcement and conditioning.
| Stuber, Garret D; Roitman, Mitchell F; Phillips, Paul E M et al. (2005) Rapid dopamine signaling in the nucleus accumbens during contingent and noncontingent cocaine administration. Neuropsychopharmacology 30:853-63 |
| Stuber, Garret D; Wightman, R Mark; Carelli, Regina M (2005) Extinction of cocaine self-administration reveals functionally and temporally distinct dopaminergic signals in the nucleus accumbens. Neuron 46:661-9 |
