Anticipation of appetitive operant action induces sustained dopamine release in the nucleus accumbens

ABSTRACT The mesolimbic dopamine system is implicated in signaling reward-related information as well as in actions that generate rewarding outcomes. These implications are commonly investigated in either Pavlovian or operant reinforcement paradigms, where only the latter requires instrumental action. To parse contributions of reward- and action-related information to dopamine signals, we directly compared the two paradigms: rats underwent either Pavlovian or operant conditioning while dopamine release was measured in the nucleus accumbens, a brain region central for processing this information. Task conditions were identical with the exception of the operant-lever response requirement. Rats in both groups released the same quantity of dopamine at the onset of the reward-predictive cue. However, only the operant-conditioning group showed a subsequent, sustained plateau in dopamine concentration throughout the entire five-second cue presentation (preceding the required action). This dopamine “ramp” was unaffected by probabilistic reward delivery, occurred exclusively prior to operant actions, and was not related to task performance or task acquisition, as it persisted throughout the two-week daily behavioral training. Instead, the ramp flexibly increased in duration with longer cue presentation, seemingly modulating the initial cue-onset triggered dopamine release (i.e., the reward-prediction error (RPE) signal), as both signal amplitude and sustain diminished when reward timing was made more predictable. Thus, our findings suggest that RPE and action components of dopamine release can be differentiated temporally into phasic and ramping/sustained signals, respectively, where the latter depends on the former and presumably reflects the anticipation or incentivization of appetitive action, conceptually akin to motivation. Significance Statement It is unclear whether the components of dopamine signals that are related to reward-associated information and reward-driven approach behavior can be separated. Most studies investigating the dopamine system utilize either Pavlovian or operant conditioning, which both involve the delivery of reward and necessitate appetitive approach behavior. Thus, used exclusively, neither paradigm can disentangle the contributions of these components to dopamine release. However, by combining both paradigms in the same study, we find that anticipation of a reward-driven operant action induces a modulation of reward-prediction-associated dopamine release, producing so-called “dopamine ramps”. Therefore, our findings provide new insight into dopamine ramps, and suggest that dopamine signals integrate reward and appetitive action in a temporally distinguishable, yet dependent, manner.