Journal
BIOLOGICAL PSYCHIATRY
Volume 81, Issue 11, Pages 941-948Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2016.12.029
Keywords
Addiction; Alcohol dependence; Functional imaging; Nalmefene; Opioid; Reward anticipation
Categories
Funding
- H. Lundbeck A/S, Valby, Denmark
- GlaxoSmithKline (GSK)
- Lundbeck
- P1vital
- Medical Research Council
- National Health Service
- Reckitt Benckiser
- Rusan Pharma
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BACKGROUND: Nalmefene is a mu and delta opioid receptor antagonist,. 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 randomized, double-blind, placebo-controlled, within-subject crossover design we aimed to determine the effect of a single dose of nalmefene on striatal blood oxygen level-dependent (BOLD) signal change during anticipation of monetary reward using the monetary incentive delay task following alcohol challenge. METHODS: Twenty-two currently heavy-drinking, non-treatment-seeking alcohol-dependent males were recruited. The effect of single dose nalmefene (18 mg) on changes in a priori defined striatal region of interest BOLD signal change during reward anticipation compared with placebo was investigated using functional magnetic resonance imaging. Both conditions were performed under intravenous alcohol administration (6% vol/vol infusion to achieve a target level of 80 mg/dL). 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 region of interest compared with placebo. Nalmefene did not alter brain perfusion. CONCLUSIONS: 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 opioid receptors, which modulate the mesolimbic dopaminergic system, and provides a neurobiological basis for its efficacy.
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