title: Distinct modulatory effects of satiety and sibutramine on brain responses to food images in humans: a double dissociation across hypothalamus, amygdala, and ventral striatum.
abstract: We used functional magnetic resonance imaging to explore brain responses to food images in overweight humans, examining independently the impact of a prescan meal ("satiety") and the anti-obesity drug sibutramine, a serotonin and noradrenaline reuptake inhibitor. We identified significantly different responses to these manipulations in amygdala, hypothalamus, and ventral striatum. Each region was specifically responsive to high-calorie compared to low-calorie food images. However, the ventral striatal response was attenuated by satiety (but unaffected by sibutramine), while the hypothalamic and amygdala responses were attenuated by drug but unaffected by satiety. Direct assessment of regional interactions confirmed the significance of this double dissociation. We explored the regional responses in greater detail by determining whether they were predictive of eating behavior and weight change. We observed that across the different regions, the individual-specific magnitude of drug- and satiety-induced modulation was associated with both variables: the sibutramine-induced modulation of the hypothalamic response was correlated with the drug's impact on both weight and subsequently measured ad libitum eating. The satiety-induced modulation of striatal response also correlated with subsequent ad libitum eating. These results suggest that hypothalamus and amygdala have roles in the control of food intake that are distinct from those of ventral striatum. Furthermore, they support a regionally specific effect on brain function through which sibutramine exerts its clinical effect.
authors.affiliation: Department of Psychiatry, University of Cambridge, GlaxoSmithKline Clinical Unit Cambridge, Addenbrooke's Centre for Clinical Investigations, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom. pcf22@cam.ac.uk
authors.forename: Paul C
authors.initials: PC
authors.lastname: Fletcher
authors.forename: Antonella
authors.initials: A
authors.lastname: Napolitano
authors.forename: Andrew
authors.initials: A
authors.lastname: Skeggs
authors.forename: Sam R
authors.initials: SR
authors.lastname: Miller
authors.forename: Bruno
authors.initials: B
authors.lastname: Delafont
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Cambridge
authors.forename: Sanne
authors.initials: S
authors.lastname: de Wit
authors.forename: Pradeep J
authors.initials: PJ
authors.lastname: Nathan
authors.forename: Allison
authors.initials: A
authors.lastname: Brooke
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: I Sadaf
authors.initials: IS
authors.lastname: Farooqi
authors.forename: Edward T
authors.initials: ET
authors.lastname: Bullmore
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000328:Adult; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D001067:Appetite Depressants / Q000494:pharmacology*; D001479:Basal Ganglia / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003503:Cyclobutanes / Q000494:pharmacology*; D004311:Double-Blind Method; D002149:Energy Intake / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005502:Food; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D050177:Overweight / Q000523:psychology; D010775:Photic Stimulation; D012528:Satiety Response / Q000502:physiology*; D055815:Young Adult
chemical_list: D001067:Appetite Depressants; D003503:Cyclobutanes; C058254:sibutramine