Physiological state tunes mesolimbic signaling: Lessons from sodium appetite and inspiration from Randall R. Sakai

Abstract

Sodium deficit poses a life-threatening challenge to body fluid homeostasis and generates a sodium appetite - the behavioral drive to ingest sodium. Dr. Randall R. Sakai greatly contributed to our understanding of the hormonal responses to negative sodium balance and to the central processing of these signals. Reactivity to the taste of sodium solutions and the motivation to seek and consume sodium changes dramatically with body fluid balance. Here, we review studies that collectively suggest that sodium deficit recruits the mesolimbic system to play a role in the behavioral expression of sodium appetite. The recruitment of the mesolimbic system likely contributes to intense sodium seeking and reinforces sodium consumption observed in deficient animals. Some of the hormones that are released in response to sodium deficit act directly on both dopamine and nucleus accumbens elements. Moreover, the taste of sodium in sodium deficient rats evokes a pattern of dopamine and nucleus accumbens activity that is similar to responses to rewarding stimuli. A very different pattern of activity is observed in non-deficient rats. Given the well-characterized endocrine response to sodium deficit and its central action, sodium appetite becomes an ideal model for understanding the role of mesolimbic signaling in reward, reinforcement and the generation of motivated behavior.

Keywords: Dopamine; Homeostasis; Motivation; Nucleus accumbens; Reward; Sodium appetite.

Fig. 1

Intra-oral infusion of 0.45 M NaCl evokes increases in NAc core dopamine release in only sodium deplete animals. (Top) Single-trial colorplots depict changes in current (color) as a function of applied electrical potential [Eapp (V); y-axis] and time (s; x-axis). Dopamine [identified by its oxidation peak (~0.6 V, green feature)] was evoked during the 4-s intra-oral infusion period (beginning at 0-s and indicated by the horizontal bar below) in sodium deplete (right) but not sodium replete (left) rats. (Bottom) Dopamine concentration changes in response to 0.45 M NaCl in sodium replete (blue) and sodium deplete (orange) rats. Concentration changes were extracted from the colorplots above. Current from the oxidation of dopamine was converted to concentration using post-recording calibration of the electrodes used during data collection.

Fig. 2

Theoretical circuit-level diagram depicting VTA inputs that drive dopamine responses in the NAc under sodium replete and deplete conditions. (Left) Under sodium replete conditions, the taste of NaCl fails to evoke an increase in NAc dopamine (blue concentration trace). The NTS represents a hypothetical path for gustatory information to influence NAc dopamine signaling. Although direct projections from the NTS to the VTA have been reported, it remains unclear if these inputs convey gustatory information. Blue arrows denote a potential route for gustatory information from the oral cavity to influence the VTA. (Right) Following sodium depletion, taste input (blue arrows) converges on the VTA with hormonal and visceral input (orange arrows) to drive increases in NAc dopamine to the taste of NaCl (orange concentration trace). Hormonal and visceral input is transmitted to the NTS through both circulation and vagal input. The NTS carries signals communicating sodium need to the pre-LC and PBel, both of which send direct projections to the VTA (orange arrows). In addition, circulating hormones may act directly on the VTA or NAc (orange circles) to gate dopamine release in response to NaCl.