Rule learning and reward contingency are associated with dissociable patterns of dopamine activation in the rat prefrontal cortex, nucleus accumbens, and dorsal striatum

Mark R. Stefani, Bita Moghaddam

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The midbrain dopamine system has been ascribed roles in reward expectancy, error detection, prediction, and memory. However, these theories typically do not differentiate between dopamine response and action in different forebrain terminal fields. We measured dopamine release in the prefrontal cortex (PFC), nucleus accumbens (NAc), and dorsal striatum (DS) of rats exposed to the same maze apparatus under three behavioral conditions: a set-shift task in which reward depended on discrimination learning and extradimensional set-shifting, a yoked condition in which reward was intermittent and not under the control of the subject, and a "reward-retrieval" variant in which reward was certain on every trial. We found dissociable patterns of dopamine release associated with learning, uncertainty, and reward. Dopamine increased in all three regions when reward was contingent on rule learning and shifting or was uncertain. These increases were sustained after behavior. There was a significant correlation between the magnitude of increase in PFC dopamine and the rapidity with which rats shifted between discrimination rules. In the yoke condition, in which the receipt of reward was always uncertain, the opposite relationship between dopamine levels and likelihood of reward was observed. Predictable, noncontingent reward was associated with increased dopamine levels in the NAc and DS. In contrast, PFC dopamine did not increase significantly above baseline levels. Thus, the dopaminergic projections to the PFC and nucleus accumbens were selectively, yet differentially, activated in situations of uncertainty and cognitive demand, whereas the dopaminergic projection to the DS responded independently of task differences in learning and reward.

Original languageEnglish (US)
Pages (from-to)8810-8818
Number of pages9
JournalJournal of Neuroscience
Issue number34
StatePublished - Aug 23 2006



  • Addiction
  • Cognition
  • Discrimination learning
  • Goal-directed behavior
  • Schizophrenia
  • Set-shift

ASJC Scopus subject areas

  • Neuroscience(all)

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