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

Efficient foraging requires an ability to coordinate discrete reward-seeking and reward-retrieval behaviors. We used pathway-specific chemogenetic inhibition to investigate how rats’ mesolimbic and mesocortical dopamine circuits contribute to the expression and modulation of reward seeking and retrieval. Inhibiting ventral tegmental area dopamine neurons disrupted the tendency for reward-paired cues to motivate reward seeking, but spared their ability to increase attempts to retrieve reward. Similar effects were produced by inhibiting dopamine inputs to nucleus accumbens, but not medial prefrontal cortex. Inhibiting dopamine neurons spared the suppressive effect of reward devaluation on reward seeking, an assay of goal-directed behavior. Attempts to retrieve reward persisted after devaluation, indicating they were habitually performed as part of a fixed action sequence. Our findings show that complete bouts of reward seeking and retrieval are behaviorally and neurally dissociable from bouts of reward seeking without retrieval. This dichotomy may prove useful for uncovering mechanisms of maladaptive behavior.


Sample-size estimation
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Replicates
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As reported in the Methods section, Experiment 2 was performed twice. It was performed in two independent cohorts of rats, each receiving intracranial injection of a viral vector obtained from a different source (i.e., UNC Chapel Hill vs. Addgene). Experiments 1, 3, and 4 were each conducted once, as stated in the methods. Exclusion of individuals was based only on histological verification of viral expression or cannula placement.

Statistical reporting
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Group allocation
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Exact p values are reported in the results and statistical tables included in supplementary information.
Rats were randomly assigned to the different viral vector groups (hM4di vs. mCherry) or cannula localization groups (NAc vs. mPFC) ahead of surgery. Experimenters were not blinded for data collection and analysis.