Persistent hunger for sodium makes brain stimulation not so sweet: Theoretical comment on Morris et al. (2006).

The nucleus accumbens is a brain region that participates in the control of behaviors related to natural reinforcers, such as ingestion, sexual behavior, incentive and instrumental learning, and that also plays a role in addictive processes. This paper comprises a review of work from our laboratory that focuses on two main research areas: (i). the role of the nucleus accumbens in food motivation, and (ii). its putative functions in cellular plasticity underlying appetitive learning. First, work within a number of different behavioral paradigms has shown that accumbens neurochemical systems play specific and dissociable roles in different aspects of food seeking and food intake, and part of this function depends on integration with the lateral hypothalamus and amygdala. We propose that the nucleus accumbens integrates information related to cognitive, sensory, and emotional processing with hypothalamic mechanisms mediating energy balance. This system as a whole enables complex hierarchical control of adaptive ingestive behavior. Regarding the second research area, our studies examining acquisition of lever-pressing for food in rats have shown that activation of glutamate N-methyl-d-aspartate (NMDA) receptors, within broadly distributed but interconnected regions (nucleus accumbens core, posterior striatum, prefrontal cortex, basolateral and central amygdala), is critical for such learning to occur. This receptor stimulation triggers intracellular cascades that involve protein phosphorylation and new protein synthesis. It is hypothesized that activity in this distributed network (including D1 receptor activity) computes coincident events and thus enhances the probability that temporally related actions and events (e.g. lever pressing and delivery of reward) become associated. Such basic mechanisms of plasticity within this reinforcement learning network also appear to be profoundly affected in addiction.

The dopamine projection to the nucleus accumbens has been implicated in behaviors directed toward the acquisition and consumption of natural rewards. The neurochemical studies that established this link made time-averaged measurements over minutes, and so the precise temporal relationship between dopamine changes and these behaviors is not known. To resolve this, we sampled dopamine every 100 msec using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in the nucleus accumbens of rats trained to press a lever for sucrose. Cues that signal the opportunity to respond for sucrose evoked dopamine release (67 +/- 20 nm) with short latency (0.2 +/- 0.1 sec onset). When the same cues were presented to rats naive to the cue-sucrose pairing, similar dopamine signals were not observed. Thus, cue-evoked increases in dopamine in trained rats reflected a learned association between the cues and sucrose availability. Lever presses for sucrose occurred at the peak of the dopamine surges. After lever presses, and while sucrose was delivered and consumed, no further increases in dopamine were detected. Rather, dopamine returned to baseline levels. Together, the results strongly implicate subsecond dopamine signaling in the nucleus accumbens as a real-time modulator of food-seeking behavior.