Nalmefene Reduces Reward Anticipation in Alcohol Dependence: An Experimental Functional Magnetic Resonance Imaging Study.

Autor: Quelch DR; Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom., Mick I; Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom., McGonigle J; Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom., Ramos AC; Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom; Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil., Flechais RSA; Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom., Bolstridge M; Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom., Rabiner E; Imanova Ltd, Centre for Imaging Sciences, London, United Kingdom; Department of Neuroimaging, Institute of Psychiatry, King's College, London, United Kingdom., Wall MB; Imanova Ltd, Centre for Imaging Sciences, London, United Kingdom., Newbould RD; Imanova Ltd, Centre for Imaging Sciences, London, United Kingdom., Steiniger-Brach B; H. Lundbeck A/S, Valby, Denmark., van den Berg F; Hammersmith Medicines Research, London, United Kingdom., Boyce M; Hammersmith Medicines Research, London, United Kingdom., Østergaard Nilausen D; H. Lundbeck A/S, Valby, Denmark., Breuning Sluth L; H. Lundbeck A/S, Valby, Denmark., Meulien D; H. Lundbeck A/S, Valby, Denmark., von der Goltz C; H. Lundbeck A/S, Valby, Denmark., Nutt D; Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom., Lingford-Hughes A; Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom. Electronic address: anne.lingford-hughes@imperial.ac.uk.
Jazyk: angličtina
Zdroj: Biological psychiatry [Biol Psychiatry] 2017 Jun 01; Vol. 81 (11), pp. 941-948. Date of Electronic Publication: 2017 Jan 10.
DOI: 10.1016/j.biopsych.2016.12.029
Abstrakt: Background: Nalmefene 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 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.
(Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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