title: The effects of the dopamine D₃ receptor antagonist GSK598809 on attentional bias to palatable food cues in overweight and obese subjects.
abstract: The mesolimbic dopamine system plays a critical role in the reinforcing effects of rewards. Evidence from pre-clinical studies suggests that D₃ receptor antagonists may attenuate the motivational impact of rewarding cues. In this study we examined the acute effects of the D₃ receptor antagonist GSK598809 on attentional bias to rewarding food cues in overweight to obese individuals (n=26, BMI mean=32.7±3.7, range 27-40 kg/m²) who reported binge and emotional eating. We also determined whether individual differences in restrained eating style modulated the effects of GSK598809 on attentional bias. The study utilized a randomized, double-blind, placebo-controlled cross-over design with each participant tested following acute administration of placebo and GSK598809 (175 mg). Attentional bias was assessed by the visual probe task and modified Stroop task using food-related words. Overall GSK598809 had no effects on attentional bias in either the visual probe or food Stroop tasks. However, the effect of GSK598809 on both visual probe and food Stroop attentional bias scores was inversely correlated with a measure of eating restraint allowing the identification of two subpopulations, low- and high-restrained eaters. Low-restrained eaters had a significant attentional bias towards food cues in both tasks under placebo, and this was attenuated by GSK598809. In contrast, high-restrained eaters showed no attentional bias to food cues following either placebo or GSK598809. These findings suggest that excessive attentional bias to food cues generated by individual differences in eating traits can be modulated by D₃ receptor antagonists, warranting further investigation with measures of eating behaviour and weight loss.
authors: Clinical Unit Cambridge, Medicines Discovery & Development, GlaxoSmithKline R&D, Cambridge, UK. pradeep.j.nathan@gsk.com
authors: Pradeep J
authors: PJ
authors: Nathan
authors: Barry V
authors: BV
authors: O'Neill
authors: Karin
authors: K
authors: Mogg
authors: Brendan P
authors: BP
authors: Bradley
authors: John
authors: J
authors: Beaver
authors: Massimo
authors: M
authors: Bani
authors: Emilio
authors: E
authors: Merlo-Pich
authors: Paul C
authors: PC
authors: Fletcher
authors: Bridget
authors: B
authors: Swirski
authors: Annelize
authors: A
authors: Koch
authors: Chris M
authors: CM
authors: Dodds
authors: Edward T
authors: ET
authors: Bullmore
mesh_terms: D000293:Adolescent; D000328:Adult; D001288:Attention / Q000187:drug effects*; D018592:Cross-Over Studies; D003463:Cues; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004311:Double-Blind Method; D005247:Feeding Behavior / Q000187:drug effects* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000523:psychology*; D050177:Overweight / Q000523:psychology*; D010775:Photic Stimulation / Q000379:methods; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors*; D057190:Stroop Test; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018492:Dopamine Antagonists; D050637:Receptors, Dopamine D3