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Comparative Study
. 2009 Jan;33(1):139-49.
doi: 10.1111/j.1530-0277.2008.00821.x. Epub 2008 Oct 31.

When what you see isn't what you get: alcohol cues, alcohol administration, prediction error, and human striatal dopamine

Karmen K Yoder  1 , Evan D Morris, Cristian C Constantinescu, Tee-Ean Cheng, Marc D Normandin, Sean J O'Connor, David A Kareken
Affiliations
Comparative Study

When what you see isn't what you get: alcohol cues, alcohol administration, prediction error, and human striatal dopamine

Karmen K Yoder et al. Alcohol Clin Exp Res. 2009 Jan.

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.

Conclusion: 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.

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Figures

Fig. 1
Fig. 1
Graphic depiction of scanning protocols. See text for details. Arrows indicate [11C]raclopride injection and beginning of image acquisition. Dotted lines represent the alcohol infusion profiles, with black box at 45 minutes indicating scan end time. (A) Baseline (BL) scan; Ringer’s solution was infused using the same infusion rate parameters determined for each subject’s alcohol scan. (B) Olfactory and visual alcohol cues (CUES) scan; the IV line was kept open during scanning, alcohol infusion was started after scanning. (C) Alcohol (EtOH) infusion scan.
Fig. 2
Fig. 2
Alcohol Urge Questionnaire (AUQ) scores before and after each scan condition. Alcohol-related cues significantly increased the postscan AUQ score.
Fig. 3
Fig. 3
Subject expectations after cue presentation.
Fig. 4
Fig. 4
Subjective High Assessment Score (SHAS) scores (mean ± SD) for high (circles, left panels) and intoxication (triangles, right panels) during the 3 scan conditions. For all scans, cue presentation began 2 minutes after [11C]raclopride injection. Ringer’s infusion (Baseline) or alcohol infusion (ETOH) began 4 minutes after [11C]raclopride injection. (Panels A, B) Baseline. (C, D) CUES. (E, F) EtOH.
Fig. 5
Fig. 5
Axial (left), coronal (middle), and sagittal (right) maps of t-values from voxel-wise statistical testing. Top: Voxel-wise 1-sample t-test to determine if ΔBPND at each voxel was significantly < 0. Dopamine levels were significantly lower during the alcohol-related cues (CUES) condition relative to the baseline (neutral cues) condition (display threshold p < 0.005). Bottom: Voxel-wise 1-sample t-test to determine if ΔBPND at each voxel was significantly >0. Dopamine levels were significantly higher during the unanticipated alcohol (EtOH) condition compared with the baseline condition (display threshold p < 0.005).
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