title: Neural and behavioral effects of a novel mu opioid receptor antagonist in binge-eating obese people.
abstract: BACKGROUND
  Binge eating is associated with obesity and has been conceptualized as "food addiction." However, this view has received only inconsistent support in humans, and limited evidence relates key neurocircuitry to the disorder. Moreover, relatively few studies have used pharmacologic functional magnetic resonance imaging to probe the underlying basis of altered eating behaviors.
  
  
  METHODS
  In a double-blind, placebo-controlled, parallel group study, we explored the effects of a potent mu-opioid receptor antagonist, GSK1521498, in obese individuals with moderate binge eating. Subjects were tested during a baseline placebo run-in period and retested after 28-days of drug (n = 21) or placebo (n = 21) treatment. Using functional magnetic resonance imaging and behavioral measures, we determined the drug's effects on brain responses to food images and, separately, on motivation to expend energy to view comparable images.
  
  
  RESULTS
  Compared with placebo, GSK1521498 was associated with a significant reduction in pallidum/putamen responses to pictures of high-calorie food and a reduction in motivation to view images of high-calorie food. Intriguingly, although motivational responding was reduced, subjective liking for the same images actually increased following drug treatment.
  
  
  CONCLUSIONS
  Stimulus-specific putamen/pallidal responses in obese people with binge eating are sensitive to altered mu-opioid function. This neuromodulation was accompanied by reductions in motivational responding, as measured by grip force, although subjective liking responses to the same stimuli actually increased. As well as providing evidence for a link between the opioid system and food-related behavior in binge-eating obese individuals, these results support a dissociation across measures of motivation and liking associated with food-related stimuli in these individuals.
authors.affiliation: Department of Psychiatry, Behavioural & Clinical Neuroscience Institute, Cambridge Biomedical Campus, University of Cambridge, United Kingdom.
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Cambridge
authors.forename: Hisham
authors.initials: H
authors.lastname: Ziauddeen
authors.forename: Pradeep J
authors.initials: PJ
authors.lastname: Nathan
authors.forename: Naresh
authors.initials: N
authors.lastname: Subramaniam
authors.forename: Chris
authors.initials: C
authors.lastname: Dodds
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Chamberlain
authors.forename: Annelize
authors.initials: A
authors.lastname: Koch
authors.forename: Kay
authors.initials: K
authors.lastname: Maltby
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Skeggs
authors.forename: Antonella
authors.initials: A
authors.lastname: Napolitano
authors.forename: I Sadaf
authors.initials: IS
authors.lastname: Farooqi
authors.forename: Edward T
authors.initials: ET
authors.lastname: Bullmore
authors.forename: Paul C
authors.initials: PC
authors.lastname: Fletcher
mesh_terms: D000293:Adolescent; D000328:Adult; D056912:Binge-Eating Disorder / Q000150:complications / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping; D004311:Double-Blind Method; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009042:Motivation / Q000187:drug effects / Q000502:physiology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D007189:Indans; C568078:N-((3,5-difluoro-3'-(1H-1,2,4-triazol-3-yl)-4-biphenylyl)methyl)-2,3-dihydro-1H-inden-2-amine; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D014230:Triazoles