Phasic mesolimbic dopamine signaling precedes and predicts performance of a self-initiated action sequence task

Biol Psychiatry. 2012 May 15;71(10):846-54. doi: 10.1016/j.biopsych.2011.12.019. Epub 2012 Feb 2.


Background: Sequential reward-seeking actions are readily learned despite the temporal gap between the earliest (distal) action in the sequence and the reward delivery. Fast dopamine signaling is hypothesized to mediate this form of learning by reporting errors in reward prediction. However, such a role for dopamine release in voluntarily initiated action sequences remains to be demonstrated.

Methods: Using fast-scan cyclic voltammetry, we monitored phasic mesolimbic dopamine release, in real time, as rats performed a self-initiated sequence of lever presses to earn sucrose rewards. Before testing, rats received either 0 (n = 11), 5 (n = 11), or 10 (n = 8) days of action sequence training.

Results: For rats acquiring the action sequence task at test, dopamine release was strongly elicited by response-contingent (but unexpected) rewards. With learning, a significant elevation in dopamine release preceded performance of the proximal action and subsequently came to precede the distal action. This predistal dopamine release response was also observed in rats previously trained on the action sequence task, and the amplitude of this signal predicted the latency with which rats completed the action sequence. Importantly, the dopamine response to contingent reward delivery was not observed in rats given extensive pretraining. Pharmacological analysis confirmed that task performance was dopamine-dependent.

Conclusions: These data suggest that phasic mesolimbic dopamine release mediates the influence that rewards exert over the performance of self-paced, sequentially-organized behavior and sheds light on how dopamine signaling abnormalities may contribute to disorders of behavioral control.

Publication types

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

MeSH terms

  • Animals
  • Conditioning, Operant / physiology*
  • Dopamine / physiology*
  • Male
  • Neostriatum / physiology*
  • Nucleus Accumbens / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement, Psychology*
  • Reward
  • Signal Transduction / physiology*


  • Dopamine