2025/08/24 by Melissa Malvaez, Andrea Suárez, Nicholas K. Griffin +3 · 1 voice
Neuroscience · Biochemistry, Genetics and Molecular Biology · #Neurotransmitter Receptor Influence on Behavior #Receptor Mechanisms and Signaling #Neuroscience and Neuropharmacology Research
paper · pdf · doi:10.1101/2025.08.22.671841
ABSTRACT Reward predictions not only promote reward pursuit, they also shape how reward is pursed. Such predictions are supported by environmental cues that signal reward availability and probability. Such cues trigger dopamine release in the nucleus accumbens core (NAc). Thus, here we used dopamine sensor fiber photometry, cell-type and pathway-specific optogenetic inhibition, Pavlovian cue–reward conditioning, and test of cue-induced reward-pursuit strategy in male and female rats, to ask whether cue-evoked phasic dopamine release is shaped by reward prediction to support reward pursuit. We found that cue-evoked NAc core dopamine is positively shaped by reward prediction and inversely relates to and predicts instrumental reward seeking. Cues that predicted imminent reward with high probability triggered a large NAc dopamine response and this was associated checking for the expected reward in the delivery location, rather than instrumental reward seeking. Cues that predicted reward with low probability elicited less dopamine and this was associated with a bias towards seeking, rather than check for reward. Correspondingly, inhibition of cue-evoked NAc dopamine increased instrumental reward-seeking and decreased reward-checking behavior. Thus, transient, cue-evoked NAc core dopamine release supports reward prediction to shape reward-pursuit strategy. SIGNIFICANCE STATEMENT Cues that signal reward availability can cause us to pursue reward. To ensure this is adaptive, we use the predictions these cues enable to help us decide how to pursue reward. When reward prediction is low, we’ll seek out new reward opportunities. When it is high, we’ll exploit the expected reward by checking for it in its usual location. Here we discovered that transient, cue-evoked nucleus accumbens dopamine fluctuations support reward predictions to shape how reward is pursued. The data show that dopamine can actually constrain reward seeking and promoting reward checking when reward is predicted strongly and imminently. These results provide new information on how dopamine shapes behavior in the moment and help understand the link between motivational and dopamine disruptions in psychiatric conditions such as addictions and depression.