Mesolimbic dopamine projections mediate cue-motivated reward seeking but not reward retrieval

Abstract

Reward-paired cues stimulate reward-seeking behavior through a combination of motivational and cognitive processes. We used pathway-specific chemogenetic inhibition of dopamine neurons to determine their role in the cue-elicited reward seeking, and applied a novel analytic approach to assay cue-induced changes in reward expectancy. Inhibiting ventral tegmental area dopamine neurons abolished cue-induced reward seeking but not reward retrieval, indicating that this pathway modulates response vigor but not reward expectancy. Locally inhibiting dopamine inputs to nucleus accumbens also disrupted cue-elicited reward seeking but not retrieval. Interestingly, the suppression produced by this treatment was greater in rats that responded to cues with exploratory reward seeking, without attempting to retrieve reward, than in rats exhibiting complete bouts of seeking with retrieval, indicating that individuals differ in their reliance on a dopamine-mediated motivational process. These findings shed new light on the behavioral and neural mechanisms of adaptive and compulsive forms of cue-motivated behavior.