title: Dopaminergic Enhancement of Striatal Response to Reward in Major Depression.
abstract: OBJECTIVE
  Major depressive disorder is characterized by reduced reward-related striatal activation and dysfunctional reward learning, putatively reflecting decreased dopaminergic signaling. The goal of this study was to test whether a pharmacological challenge designed to facilitate dopaminergic transmission can enhance striatal responses to reward and improve reward learning in depressed individuals.
  
  
  METHODS
  In a double-blind placebo-controlled design, 46 unmedicated depressed participants and 43 healthy control participants were randomly assigned to receive either placebo or a single low dose (50 mg) of the D2/D3receptor antagonist amisulpride, which is believed to increase dopamine signaling through presynaptic autoreceptor blockade. To investigate the effects of increased dopaminergic transmission on reward-related striatal function and behavior, a monetary incentive delay task (in conjunction with functional MRI) and a probabilistic reward learning task were administered at absorption peaks of amisulpride.
  
  
  RESULTS
  Depressed participants selected previously rewarded stimuli less frequently than did control participants, indicating reduced reward learning, but this effect was not modulated by amisulpride. Relative to depressed participants receiving placebo (and control participants receiving amisulpride), depressed participants receiving amisulpride exhibited increased striatal activation and potentiated corticostriatal functional connectivity between the nucleus accumbens and the midcingulate cortex in response to monetary rewards. Stronger corticostriatal connectivity in response to rewards predicted better reward learning among depressed individuals receiving amisulpride as well as among control participants receiving placebo.
  
  
  CONCLUSIONS
  Acute enhancement of dopaminergic transmission potentiated reward-related striatal activation and corticostriatal functional connectivity in depressed individuals but had no behavioral effects. Taken together, the results suggest that targeted pharmacological treatments may normalize neural correlates of reward processing in depression; despite such acute effects on neural function, behavioral modification may require more chronic exposure. This is consistent with previous reports that antidepressant effects of amisulpride in depression emerged after sustained administration.
authors: From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.
authors: Roee
authors: R
authors: Admon
authors: From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.
authors: Roselinde H
authors: RH
authors: Kaiser
authors: From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.
authors: Daniel G
authors: DG
authors: Dillon
authors: From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.
authors: Miranda
authors: M
authors: Beltzer
authors: From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.
authors: Franziska
authors: F
authors: Goer
authors: From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.
authors: David P
authors: DP
authors: Olson
authors: From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.
authors: Gordana
authors: G
authors: Vitaliano
authors: From the Center for Depression, Anxiety, and Stress Research and the McLean Imaging Center, McLean Hospital, Belmont, Mass.; and the Department of Psychiatry, Harvard Medical School, Boston.
authors: Diego A
authors: DA
authors: Pizzagalli
mesh_terms: D000328:Adult; D000077582:Amisulpride; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology*; D003463:Cues; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology* / Q000517:prevention & control; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000627:therapeutic use*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000502:physiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009042:Motivation / Q000187:drug effects / Q000502:physiology; D012201:Reward; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology*
chemical_list: D018492:Dopamine Antagonists; D013469:Sulpiride; D000077582:Amisulpride; D004298:Dopamine
keywords: Antidepressants; Biological Markers; Brain Imaging Techniques; Dopamine; Mood Disorders-Unipolar; Reward