Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Feb;41(4):477-86.
doi: 10.1111/ejn.12802. Epub 2014 Dec 26.

Chronic alcohol intake abolishes the relationship between dopamine synthesis capacity and learning signals in the ventral striatum

Lorenz Deserno  1 , Anne Beck, Quentin J M Huys, Robert C Lorenz, Ralph Buchert, Hans-Georg Buchholz, Michail Plotkin, Yoshitaka Kumakara, Paul Cumming, Hans-Jochen Heinze, Anthony A Grace, Michael A Rapp, Florian Schlagenhauf, Andreas Heinz
Affiliations

Chronic alcohol intake abolishes the relationship between dopamine synthesis capacity and learning signals in the ventral striatum

Lorenz Deserno et al. Eur J Neurosci. 2015 Feb.

Abstract

Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug-related stimuli towards drug-related stimuli. Such 'hijacked' dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N = 27). All participants also underwent 6-[(18) F]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation by RPEs nor striatal dopamine synthesis capacity differed between groups. However, ventral striatal coding of RPEs correlated inversely with craving in patients. Furthermore, we found a negative correlation between ventral striatal coding of RPEs and dopamine synthesis capacity in healthy controls, but not in alcohol-dependent patients. Moderator analyses showed that the magnitude of the association between dopamine synthesis capacity and RPE coding depended on the amount of chronic, habitual alcohol intake. Despite the relatively small sample size, a power analysis supports the reported results. Using a multimodal imaging approach, this study suggests that dopaminergic modulation of neural learning signals is disrupted in alcohol dependence in proportion to long-term alcohol intake of patients. Alcohol intake may perpetuate itself by interfering with dopaminergic modulation of neural learning signals in the ventral striatum, thus increasing craving for habitual drug intake.

Keywords: PET; alcohol addiction; dopamine; fMRI; prediction error.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Reversal learning task
During fMRI acquisition, participants performed two sessions of 100 trials with three types of blocks: in block type 1, for the right-hand stimulus a reward (green smiley) was delivered in 80% of the recent right-hand choices, and a punishment (red frowny) delivered otherwise. In block type 2, the contingencies were simply reversed for the left and right sides. Reversals always occurred after 16 trials, or any time after 10 trials once subjects reached 70% correct choices.
Figure 2
Figure 2. Negative correlation of ventral striatal reward prediction errors and craving in patients
In alcohol-dependent patients, mean parameter estimates of the prediction error contrast were extracted for the literature-based volume of interest of the right ventral striatum and correlated with craving scores (r=−.53, p<.05 one-tailed).
Figure 3
Figure 3. Disrupted dopaminergic regulation of reward prediction errors in right ventral striatum of alcohol-dependent patients
A SPM design matrix and contrast weights for the group × covariate (right ventral striatal FDOPA Kinapp) interaction. B Voxelwise map of the group × covariate contrast at y = 16, thresholded at T > 2.5 for display purposes; this reached significance in right ventral striatum (x=14.5, y=13, z=−5: t=3.32, FWE-corrected for ventral striatum p<.05). C Scatterplot of the group x covariate interaction for visualization with controls as asterisks and patients as circles. Reward prediction errors (mean parameter estimates) and dopamine synthesis capacity were extracted using the literature-based right ventral striatal volume of interest of interest.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Anton RF. Obsessive-compulsive aspects of craving: development of the Obsessive Compulsive Drinking Scale. Addiction. 2000;95(Suppl 2):S211–217. - PubMed
    1. Ashburner J, Friston KJ. Unified segmentation. Neuroimage. 2005;26:839–851. - PubMed
    1. Bayer HM, Glimcher PW. Midbrain dopamine neurons encode a quantitative reward prediction error signal. Neuron. 2005;47:129–141. - PMC - PubMed
    1. Beck A, Wustenberg T, Genauck A, Wrase J, Schlagenhauf F, Smolka MN, Mann K, Heinz A. Effect of brain structure, brain function, and brain connectivity on relapse in alcohol-dependent patients. Arch Gen Psychiatry. 2012;69:842–852. - PubMed
    1. Belin D, Everitt BJ. Cocaine seeking habits depend upon dopamine-dependent serial connectivity linking the ventral with the dorsal striatum. Neuron. 2008;57:432–441. - PubMed

Publication types