title: When what you see isn't what you get: alcohol cues, alcohol administration, prediction error, and human striatal dopamine.
abstract: BACKGROUND
  The mesolimbic dopamine (DA) system is implicated in the development and maintenance of alcohol drinking; however, the exact mechanisms by which DA regulates human alcohol consumption are unclear. This study assessed the distinct effects of alcohol-related cues and alcohol administration on striatal DA release in healthy humans.
  
  
  METHODS
  Subjects underwent 3 PET scans with [(11)C]raclopride (RAC). Subjects were informed that they would receive either an IV Ringer's lactate infusion or an alcohol (EtOH) infusion during scanning, with naturalistic visual and olfactory cues indicating which infusion would occur. Scans were acquired in the following sequence: (1) Baseline Scan: Neutral cues predicting a Ringer's lactate infusion, (2) CUES Scan: Alcohol-related cues predicting alcohol infusion in a Ringer's lactate solution, but with alcohol infusion after scanning to isolate the effects of cues, and (3) EtOH Scan: Neutral cues predicting Ringer's, but with alcohol infusion during scanning (to isolate the effects of alcohol without confounding expectation or craving).
  
  
  RESULTS
  Relative to baseline, striatal DA concentration decreased during CUES, but increased during EtOH.
  
  
  CONCLUSIONS
  While the results appear inconsistent with some animal experiments showing dopaminergic responses to alcohol's conditioned cues, they can be understood in the context of the hypothesized role of the striatum in reward prediction error, and of animal studies showing that midbrain dopamine neurons decrease and increase firing rates during negative and positive prediction errors, respectively. We believe that our data are the first in humans to demonstrate such changes in striatal DA during reward prediction error.
authors.affiliation: Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Karmen K
authors.initials: KK
authors.lastname: Yoder
authors.forename: Evan D
authors.initials: ED
authors.lastname: Morris
authors.forename: Cristian C
authors.initials: CC
authors.lastname: Constantinescu
authors.forename: Tee-Ean
authors.initials: TE
authors.lastname: Cheng
authors.forename: Marc D
authors.initials: MD
authors.lastname: Normandin
authors.forename: Sean J
authors.initials: SJ
authors.lastname: O'Connor
authors.forename: David A
authors.initials: DA
authors.lastname: Kareken
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000378:metabolism* / Q000523:psychology; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D003463:Cues; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D010775:Photic Stimulation / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods; D011237:Predictive Value of Tests; D012107:Research Design; D055815:Young Adult
chemical_list: D000431:Ethanol; D004298:Dopamine