The nucleus accumbens is a pivotal component of the brain circuit underlying reward and motivated behavior, including the positive reinforcement that contributes to alcohol use. My experiments examine nucleus accumbens core and shell function during ethanol reinforcement in rats, with particular focus on how dopamine input modulates accumbal activity on the millisecond timescale. I use two approaches: electrophysiological firing patterns of neurons in the nucleus accumbens are evaluated using multi-electrode arrays, and phasic (subsecond) dopamine activity is evaluated using fast-scan cyclic voltammetry.
Electrophysiological firing patterns of neurons in the nucleus accumbens. Many aspects of goal-directed behaviors and conditioned stimuli associated with ethanol drinking in rats are reflected in vivo in the electrophysiological firing patterns of medium spiny neurons in the nucleus accumbens as transient excitations or inhibitions that are time-locked to operant events. My data reveal that while nucleus accumbens neurons show the same types of firing patterns for ethanol and water reinforcement, the majority of these phasic cells are selective for one or the other reinforcer, a phenomenon previously reported for cocaine versus water (Carelli et al., J. Neurosci., 2000). I am currently investigating how plastic these reinforcer-specific neurons may be to changes in motivational state or pharmacological challenge. The clinical implication of functionally separate circuits encoding ethanol versus other reinforcers is that circuits underlying ethanol self-administration might be therapeutically targeted.
Subsecond dopamine fluctuations in the nucleus accumbens. The mesolimbic dopamine input to the nucleus accumbens is well known to be involved in reinforcement and addiction. By using fast-scan cyclic voltammetry, I can measure endogenous dopamine fluctuations in awake and behaving rats. My data have demonstrated that transient dopamine signals occur throughout the dorsal and ventral striatum under basal conditions and increase when salient stimuli (another rat, food treat) are introduced into the experimental chamber. I am currently measuring dopamine transients in rats self-administering alcohol and water in an operant setting, and find that dopamine signals can be time-locked to cues predicting reinforcer availability and to the lever presses.