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

Elife. 2019 May 20;8:e43551. doi: 10.7554/eLife.43551.


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.

Keywords: DREADD; Pavlovian instrumental transfer; action chunking; decision making; dopamine; motivation; neuroscience; rat.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Conditioning, Operant / physiology
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacology
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / physiology
  • Motivation / drug effects
  • Motivation / physiology*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiology*
  • Prefrontal Cortex / drug effects
  • Rats
  • Reward
  • Ventral Tegmental Area / physiology


  • Dopamine Antagonists
  • Dopamine