Role of dopamine D2 receptors in human reinforcement learning

Neuropsychopharmacology. 2014 Sep;39(10):2366-75. doi: 10.1038/npp.2014.84. Epub 2014 Apr 9.


Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, whereas loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Choice Behavior / drug effects
  • Choice Behavior / physiology
  • Dopamine Antagonists / blood
  • Dopamine Antagonists / pharmacology
  • Double-Blind Method
  • Genotype
  • Genotyping Techniques
  • Humans
  • Male
  • Models, Psychological
  • Neuropsychological Tests
  • Polymorphism, Genetic
  • Prolactin / blood
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3 / antagonists & inhibitors
  • Receptors, Dopamine D3 / metabolism
  • Reinforcement, Psychology*
  • Sulpiride / blood
  • Sulpiride / pharmacology
  • Young Adult


  • DRD2 protein, human
  • Dopamine Antagonists
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Sulpiride
  • Prolactin