The International Journal of Neuropsychopharmacology

Table of Contents - March 2012 - Volume 15, Issue 02 (Thematic Section: Eating Disorders and Obesity)  

Thematic Section: Eating Disorders and Obesity

The effects of the dopamine D3 receptor antagonist GSK598809 on attentional bias to palatable food cues in overweight and obese subjects

Pradeep J. Nathana1a2 c1*, Barry V. O'Neilla1*, Karin Mogga3*, Brendan P. Bradleya3*, John Beavera4, Massimo Bania5, Emilio Merlo-Picha5, Paul C. Fletchera2, Bridget Swirskia1†, Annelize Kocha1, Chris M. Doddsa1* and Edward T. Bullmorea1a2

a1 Clinical Unit Cambridge, Medicines Discovery & Development, GlaxoSmithKline R&D, Cambridge, UK

a2 Brain Mapping Unit, Department of Psychiatry, University of Cambridge, UK

a3 School of Psychology, University of Southampton, UK

a4 Clinical Imaging Centre (CIC), Medicines Discovery & Development, GlaxoSmithKline R&D, London, UK

a5 Neurosciences CEDD, Medicines Discovery & Development, GlaxoSmithKline R&D, Verona, Italy

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.

(Received February 24 2011)

(Reviewed April 13 2011)

(Revised June 02 2011)

(Accepted June 09 2011)

(Online publication July 12 2011)

Key Words:

Correspondence:

c1 Address for correspondence: Professor P. J. Nathan, GSK Clinical Unit Cambridge, Addenbrooke's Centre for Clinical Investigations, Cambridge Biomedical Campus, Cambridge CB2 2GG, UK. Tel.: +44 1223 296081 Fax: +44 1223 296108 Email: pradeep.j.nathan@gsk.com

Footnotes

* These authors contributed equally to this work.

† This paper is dedicated to Bridget Swirski, who sadly passed away during the preparation of this manuscript.

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