title: Nalmefene Reduces Reward Anticipation in Alcohol Dependence: An Experimental Functional Magnetic Resonance Imaging Study.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Quelch
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom.
authors.forename: Inge
authors.initials: I
authors.lastname: Mick
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: McGonigle
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom; Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Ramos
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom.
authors.forename: Remy S A
authors.initials: RSA
authors.lastname: Flechais
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Bolstridge
authors.affiliation: Imanova Ltd, Centre for Imaging Sciences, London, United Kingdom; Department of Neuroimaging, Institute of Psychiatry, King's College, London, United Kingdom.
authors.forename: Eugenii
authors.initials: E
authors.lastname: Rabiner
authors.affiliation: Imanova Ltd, Centre for Imaging Sciences, London, United Kingdom.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Wall
authors.affiliation: Imanova Ltd, Centre for Imaging Sciences, London, United Kingdom.
authors.forename: Rexford D
authors.initials: RD
authors.lastname: Newbould
authors.affiliation: H. Lundbeck A/S, Valby, Denmark.
authors.forename: Björn
authors.initials: B
authors.lastname: Steiniger-Brach
authors.affiliation: Hammersmith Medicines Research, London, United Kingdom.
authors.forename: Franz
authors.initials: F
authors.lastname: van den Berg
authors.affiliation: Hammersmith Medicines Research, London, United Kingdom.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Boyce
authors.affiliation: H. Lundbeck A/S, Valby, Denmark.
authors.forename: Dorrit
authors.initials: D
authors.lastname: Østergaard Nilausen
authors.affiliation: H. Lundbeck A/S, Valby, Denmark.
authors.forename: Lasse
authors.initials: L
authors.lastname: Breuning Sluth
authors.affiliation: H. Lundbeck A/S, Valby, Denmark.
authors.forename: Didier
authors.initials: D
authors.lastname: Meulien
authors.affiliation: H. Lundbeck A/S, Valby, Denmark.
authors.forename: Christoph
authors.initials: C
authors.lastname: von der Goltz
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Nutt
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, United Kingdom. Electronic address: anne.lingford-hughes@imperial.ac.uk.
authors.forename: Anne
authors.initials: A
authors.lastname: Lingford-Hughes
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000437:Alcoholism / Q000097:blood / Q000523:psychology*; D059031:Anticipation, Psychological / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D004311:Double-Blind Method; D004357:Drug Synergism; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D012201:Reward
chemical_list: D009292:Narcotic Antagonists; D000431:Ethanol; D009271:Naltrexone; C038981:nalmefene
keywords: Addiction; Alcohol dependence; Functional imaging; Nalmefene; Opioid; Reward anticipation