title: Effects of mu opioid receptor antagonism on cognition in obese binge-eating individuals.
abstract: BACKGROUND
  Translational research implicates the mu opioid neurochemical system in hedonic processing, but its role in dissociable high-level cognitive functions is not well understood. Binge-eating represents a useful model of 'behavioural addiction' for exploring this issue.
  
  
  OBJECTIVE
  The aim of this study was to objectively assess the cognitive effects of a mu opioid receptor antagonist in obese individuals with binge-eating symptoms.
  
  
  METHODS
  Adults with moderate to severe binge-eating and body mass index ≥30 kg/m² received 4 weeks of treatment with a mu opioid receptor antagonist (GSK1521498) 2 or 5 mg per day, or placebo, in a double-blind randomised parallel design. Neuropsychological assessment was undertaken at baseline and endpoint to quantify processing bias for food stimuli (visual dot probe with 500- and 2,000-ms stimulus presentations and food Stroop tasks) and other distinct cognitive functions (N-back working memory, sustained attention, and power of attention tasks).
  
  
  RESULTS
  GSK1521498 5 mg/day significantly reduced attentional bias for food cues on the visual dot probe task versus placebo (p = 0.042), with no effects detected on other cognitive tasks (all p > 0.10). The effect on attentional bias was limited to the longer stimulus duration condition in the higher dose cohort alone.
  
  
  CONCLUSIONS
  These findings support a central role for mu opioid receptors in aspects of attentional processing of food cues but militate against the notion of major modulatory influences of mu opioid receptors in working memory and sustained attention. The findings have implications for novel therapeutic directions and suggest that the role of different opioid receptors in cognition merits further research.
authors: Clinical Unit Cambridge, GlaxoSmithKline, Addenbrooke's Hospital, Cambridge CB0 0QQ, UK. srchamb@gmail.com
authors: Samuel R
authors: SR
authors: Chamberlain
authors: Karin
authors: K
authors: Mogg
authors: Brendan P
authors: BP
authors: Bradley
authors: Annelize
authors: A
authors: Koch
authors: Chris M
authors: CM
authors: Dodds
authors: Wenli X
authors: WX
authors: Tao
authors: Kay
authors: K
authors: Maltby
authors: Bhopinder
authors: B
authors: Sarai
authors: Antonella
authors: A
authors: Napolitano
authors: Duncan B
authors: DB
authors: Richards
authors: Edward T
authors: ET
authors: Bullmore
authors: Pradeep J
authors: PJ
authors: Nathan
mesh_terms: D000293:Adolescent; D000328:Adult; D001288:Attention; D056912:Binge-Eating Disorder / Q000188:drug therapy* / Q000523:psychology; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D009483:Neuropsychological Tests; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D012720:Severity of Illness Index; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
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