Two-week administration of the combined serotonin-noradrenaline reuptake inhibitor duloxetine augments functioning of mesolimbic incentive processing circuits

Biol Psychiatry. 2011 Sep 15;70(6):568-74. doi: 10.1016/j.biopsych.2011.03.041. Epub 2011 May 24.


Background: Anhedonia and lack of motivation are core symptoms of major depressive disorder (MDD). Neuroimaging studies in MDD patients have shown reductions in reward-related activity in terminal regions of the mesolimbic dopamine (DA) system, such as the ventral striatum. Monoamines have been implicated in both mesolimbic incentive processing and the mechanism of action of antidepressant drugs. However, not much is known about antidepressant effects on mesolimbic incentive processing in humans, which might be related to the effects on anhedonia.

Methods: To investigate the short-term effects of antidepressants on reward-related activity in the ventral striatum, we investigated the effect of the combined serotonin-norepinephrine reuptake inhibitor duloxetine. Healthy volunteers underwent functional magnetic resonance imaging in a randomized, double-blind, placebo-controlled, crossover study. After taking duloxetine (60 mg once a day) or placebo for 14 days, participants completed a monetary incentive delay task that activates the ventral striatum during reward anticipation.

Results: Our results (n = 19) show enhanced ventral striatal responses after duloxetine administration compared with placebo. Moreover, this increase in ventral striatal activity was positively correlated with duloxetine plasma levels.

Conclusions: This is the first study to demonstrate that antidepressants augment neural activity in mesolimbic DA incentive processing circuits in healthy volunteers. These effects are likely caused by the increase in monoamine neurotransmission in the ventral striatum. Our findings suggest that antidepressants may alleviate anhedonia by stimulating incentive processing.

Publication types

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

MeSH terms

  • Adolescent
  • Adrenergic Uptake Inhibitors / blood
  • Adrenergic Uptake Inhibitors / pharmacology*
  • Adult
  • Affect / physiology
  • Brain Mapping / methods
  • Brain Mapping / psychology
  • Duloxetine Hydrochloride
  • Female
  • Humans
  • Limbic System / drug effects
  • Limbic System / physiology*
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Imaging / psychology
  • Male
  • Mesencephalon / drug effects
  • Mesencephalon / physiology*
  • Middle Aged
  • Motivation / drug effects*
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Neuroimaging / methods
  • Neuroimaging / psychology
  • Psychomotor Performance / physiology*
  • Reward
  • Selective Serotonin Reuptake Inhibitors / blood
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Thiophenes / blood
  • Thiophenes / pharmacology*


  • Adrenergic Uptake Inhibitors
  • Serotonin Uptake Inhibitors
  • Thiophenes
  • Duloxetine Hydrochloride