Delays conferred by escalating costs modulate dopamine release to rewards but not their predictors.

Efficient reward seeking is essential for survival and invariably requires overcoming costs, such as physical effort and delay, which are constantly changing in natural settings. Dopamine transmission has been implicated in decisions weighing the benefits and costs of obtaining a reward, but it is still unclear how dynamically changing effort and delay costs affect dopamine signaling to rewards and related stimuli. Using fast-scan cyclic voltammetry, we examined phasic dopamine release in the nucleus accumbens (NAcc) core and shell during reward-seeking behavior in rats. To manipulate the effort and time needed to earn a reward, we used instrumental tasks in which the response requirements (number of lever presses) were either fixed throughout a behavioral session [fixed ratio (FR)] or systematically increased from trial to trial [progressive ratio (PR)]. Dopamine release evoked by cues denoting reward availability was no different between these conditions, indicating insensitivity to escalating effort or delay costs. In contrast, dopamine release to reward delivery in both the NAcc core and shell increased in PR, but not in FR, sessions. This enhancement of reward-evoked dopamine signaling was also observed in sessions in which the response requirement was fixed but the delay to reward delivery increased, yoked to corresponding trials in PR sessions. These findings suggest that delay, and not effort, was principally responsible for the increased reward-evoked dopamine release in PR sessions. Together, these data demonstrate that NAcc dopamine release to rewards and their predictors are dissociable and differentially regulated by the delays conferred under escalating costs.