Nalmefene reduces reward anticipation in alcohol dependence: an experimental functional magnetic resonance imaging study
File(s)
Supporting information
Accepted version
Author(s)
Type
Journal Article
Abstract
Background
Nalmefene (Selincro®) is a µ- and δ- opioid receptor antagonist, κ-opioid receptor partial agonist that has recently been approved in Europe for treating alcohol dependence. It offers a treatment approach for alcohol dependent individuals with “high risk drinking levels” to reduce their alcohol consumption. However, the neurobiological mechanism underpinning its effects on alcohol consumption remains to be determined. Using a randomised, double blind, placebo controlled within subject cross-over design we aimed to determine the effect of a single dose of nalmefene on striatal BOLD (blood oxygen level dependent) signal change during anticipation of monetary reward using the Monetary Incentive Delay Task following alcohol challenge.
Methods and Materials
22 currently heavy drinking, non-treatment seeking alcohol dependent males were recruited. The effect of single dose nalmefene (18mg; Selincro®) on changes in a priori defined striatal region of interest (ROI) BOLD signal change during reward anticipation compared with placebo were investigated using functional MRI (magnetic resonance imaging). Both conditions were performed under intravenous alcohol administration (6% v/v infusion to achieve a target level of 80mg%).
Results
Datasets from 18 participants were available and showed that in the presence of the alcohol infusion, nalmefene significantly reduced the BOLD response in the striatal ROI compared with placebo. Nalmefene did not alter brain perfusion.
Discussion
Nalmefene blunts BOLD response in the mesolimbic system during anticipation of monetary reward and an alcohol infusion. This is consistent with nalmefene’s actions on opiate receptors, which modulate the mesolimbic dopaminergic system, and provides a neurobiological basis for its efficacy.
Nalmefene (Selincro®) is a µ- and δ- opioid receptor antagonist, κ-opioid receptor partial agonist that has recently been approved in Europe for treating alcohol dependence. It offers a treatment approach for alcohol dependent individuals with “high risk drinking levels” to reduce their alcohol consumption. However, the neurobiological mechanism underpinning its effects on alcohol consumption remains to be determined. Using a randomised, double blind, placebo controlled within subject cross-over design we aimed to determine the effect of a single dose of nalmefene on striatal BOLD (blood oxygen level dependent) signal change during anticipation of monetary reward using the Monetary Incentive Delay Task following alcohol challenge.
Methods and Materials
22 currently heavy drinking, non-treatment seeking alcohol dependent males were recruited. The effect of single dose nalmefene (18mg; Selincro®) on changes in a priori defined striatal region of interest (ROI) BOLD signal change during reward anticipation compared with placebo were investigated using functional MRI (magnetic resonance imaging). Both conditions were performed under intravenous alcohol administration (6% v/v infusion to achieve a target level of 80mg%).
Results
Datasets from 18 participants were available and showed that in the presence of the alcohol infusion, nalmefene significantly reduced the BOLD response in the striatal ROI compared with placebo. Nalmefene did not alter brain perfusion.
Discussion
Nalmefene blunts BOLD response in the mesolimbic system during anticipation of monetary reward and an alcohol infusion. This is consistent with nalmefene’s actions on opiate receptors, which modulate the mesolimbic dopaminergic system, and provides a neurobiological basis for its efficacy.
Date Issued
2017-01-10
Date Acceptance
2017-01-09
Citation
Biological Psychiatry, 2017, 81 (11), pp.941-948
ISSN
1873-2402
Publisher
Elsevier
Start Page
941
End Page
948
Journal / Book Title
Biological Psychiatry
Volume
81
Issue
11
Copyright Statement
© 2017 Society of Biological Psychiatry. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Subjects
Addiction
Alcohol dependence
Functional imaging
Nalmefene
Opioid
Reward anticipation
Psychiatry
06 Biological Sciences
17 Psychology And Cognitive Sciences
11 Medical And Health Sciences
Publication Status
Published