Nucleus accumbens core dopamine signaling tracks the need-based motivational value of food-paired cues

Abstract

Environmental reward-predictive stimuli provide a major source of motivation for instrumental reward-seeking activity and this has been linked to dopamine signaling in the nucleus accumbens (NAc) core. This cue-induced incentive motivation can be quite general, not restricted to instrumental actions that earn the same unique reward, and is also typically regulated by one's current need state, such that cues only motivate actions when this is adaptive. But it remains unknown whether cue-evoked dopamine signaling is similarly regulated by need state. Here, we used fast-scan cyclic voltammetry to monitor dopamine concentration changes in the NAc core of rats during a Pavlovian-to-instrumental transfer task in which the motivating influence of two cues, each signaling a distinct food reward (sucrose or food pellets), over an action earning a third unique food reward (polycose) was assessed in a state of hunger and of satiety. Both cues elicited a robust NAc dopamine response when hungry. The magnitude of the sucrose cue-evoked dopamine response correlated with the Pavlovian-to-instrumental transfer effect that was selectively induced by this stimulus. Satiety attenuated these cue-evoked dopamine responses and behavioral responding, even though rats had never experienced the specific food rewards in this state. These data demonstrate that cue-evoked NAc core responses are sensitive to current need state, one critical variable that determines the current adaptive utility of cue-motivated behavior. Food-predictive stimuli motivate food-seeking behavior. Here, we show that food cues evoke a robust nucleus accumbens core dopamine response when hungry that correlates with the cue's ability to invigorate general food seeking. This response is attenuated when sated, demonstrating that food cue-evoked accumbens dopamine responses are sensitive to the need state information that determines the current adaptive utility of cue-motivated action.

Keywords: Pavlovian-to-instrumental transfer; hunger; mesolimbic dopamine; reward; satiety; voltammetry.

Figure 1. Task design and behavioral results

A. Schematic representation of recording sites in NAc core. Line drawing of coronal section is reprinted from (Paxinos & Watson 1998), +1.3 mm from bregma. All placements shown in the left hemisphere, but 2 of the 8 recordings were from the right hemisphere. B. Experimental Design. Rats were first given Pavlovian training to associate each of two auditory cues with one of two unique food rewards, sucrose solution (CS_Suc) or food pellets (CS_Pel). In the second phase of training, rats were given instrumental training to learn to lever press (LP) to earn a grape-flavored polycose solution (Poly). Rats were then given a Pavlovian-to-instrumental transfer (PIT) test under a state of either hunger or satiety in to assess the influence of CS presentation on lever pressing. C. The PIT effect. Number of lever presses during each 2-min CS period, averaged across trials compared between the CS-free (PreCS) and CS periods. D. Conditioned food-port approach responding. Number entries into the food-delivery port during each 2-min CS period, averaged across trials compared between the PreCS and CS periods. Error bars indicate ±1 SEM. ^*p<0.05, ^***p<0.001 relative to PreCS control period. #p<0.05, ^###p<0.001 relative to same period during hungry test.

Figure 2. Cue-induced dopamine concentration changes in the nucleus accumbens core during Pavlovian-to-instrumental transfer

A & C. Representative, single-trial dopamine concentration v. time traces during the hungry (A) and sated (C) PIT test from the same rat 10 s before and during the entire 2-min PreCS period (gray) and presentation of the CS_Suc (blue) and CS_Pel (brown). Asterisks mark fluctuations in dopamine that reached threshold for designation as dopamine transients. Scale bar to the lower right represents 20 nM dopamine concentration change. Insets show background-subtracted CVs showing oxidation and reduction peaks that identify the detected electrochemical signal as dopamine, taken from within the first 10 s following CS onset. B. & D. Group-averaged dopamine concentration change during the CS_Suc, CS_Pel, and control PreCS period. Shading reflects +1 between-subject SEM. Scale bar represents 5 nM dopamine concentration change. E. Peak dopamine concentration change in the 10-s period following CS onset. F. Correlation between peak dopamine concentration change at CS onset and the average CS-induced change in lever pressing for the hungry (left) and sated (right) PIT test. Regression line with 95% confidence bands are shown. G. Average number of dopamine transients per 2-min period. Error bars indicate ±1 SEM. ^*p<0.05, ^**p<0.01, ^***p<0.001 relative to PreCS control period. #p<0.05, ^###p<0.001 relative to same period during hungry test.