Dopaminergic modulation of the human reward system: a placebo-controlled dopamine depletion fMRI study

J Psychopharmacol. 2011 Apr;25(4):538-49. doi: 10.1177/0269881110367731. Epub 2010 Jun 8.


Reward related behaviour is linked to dopaminergic neurotransmission. Our aim was to gain insight into dopaminergic involvement in the human reward system. Combining functional magnetic resonance imaging with dopaminergic depletion by α-methylparatyrosine we measured dopamine-related brain activity in 10 healthy volunteers. In addition to blood-oxygen-level-dependent (BOLD) contrast we assessed the effect of dopaminergic depletion on prolactin response, peripheral markers for dopamine and norepinephrine. In the placebo condition we found increased activation in the left caudate and left cingulate gyrus during anticipation of reward. In the α-methylparatyrosine condition there was no significant brain activation during anticipation of reward or loss. In α-methylparatyrosine, anticipation of reward vs. loss increased activation in the right insula, left frontal, right parietal cortices and right cingulate gyrus. Comparing placebo versus α-methylparatyrosine showed increased activation in the left cingulate gyrus during anticipation of reward and the left medial frontal gyrus during anticipation of loss. α-methylparatyrosine reduced levels of dopamine in urine and homovanillic acid in plasma and increased prolactin. No significant effect of α-methylparatyrosine was found on norepinephrine markers. Our findings implicate distinct patterns of BOLD underlying reward processing following dopamine depletion, suggesting a role of dopaminergic neurotransmission for anticipation of monetary reward.

Publication types

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

MeSH terms

  • Adult
  • Behavior
  • Brain / drug effects
  • Brain / physiology*
  • Dopamine / metabolism*
  • Dopamine / urine
  • Double-Blind Method
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / blood
  • Enzyme Inhibitors / metabolism*
  • Gyrus Cinguli / physiology
  • Homovanillic Acid / blood*
  • Homovanillic Acid / urine
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging / methods
  • Male
  • Norepinephrine / blood*
  • Norepinephrine / metabolism
  • Prolactin / blood
  • Prolactin / metabolism
  • Reward*
  • Young Adult
  • alpha-Methyltyrosine / administration & dosage*
  • alpha-Methyltyrosine / blood


  • Enzyme Inhibitors
  • alpha-Methyltyrosine
  • Prolactin
  • Dopamine
  • Norepinephrine
  • Homovanillic Acid