Circadian modulation of dopamine release shapes reward-evoked signaling in the nucleus accumbens

ABSTRACT The circadian system is an important regulator of reward-related neural function and behavior. Dopamine (DA) release in the nucleus accumbens is a key component of reward processing, yet how circadian timing shapes DA release in relation to reward behavior remains unclear. Here, we investigated circadian rhythms in DA release and reward behavior using long-term fiber photometry paired with an automated reward delivery and measurement system. We found two distinct circadian rhythms in DA release: spontaneous DA, reflecting ongoing DA release not associated with reward, and reward-evoked DA, reflecting transient DA response during reward. Spontaneous DA peaked during the early subjective day, whereas reward-evoked peak DA peaked near the day-to-night transition. Both rhythms were distinct from reward behavior, which peaked during the early subjective night. Linear modeling further showed that the relationship between reward-evoked DA and reward behavior depended on circadian time, with greater DA responses occurring between late subjective day and early subjective night. Spontaneous baseline and reward-evoked DA were also negatively correlated, and this relationship was likewise modulated across circadian time. Together, these findings support a model in which circadian modulation of baseline DA may alter the gain of reward-evoked signaling, amplifying DA responses across behaviorally relevant times of day.