Obesity is associated with high serotonin 4 receptor availability in the brain reward circuitry.
The neurobiology underlying obesity is not fully understood. The neurotransmitter serotonin (5-HT) is established as a satiety-generating signal, but its rewarding role in feeding is less well elucidated. From animal experiments there is now evidence that the 5-HT(4) receptor (5-HT(4)R) is involved in food intake, and that pharmacological or genetic manipulation of the receptor in reward-related brain areas alters food intake. Here, we used positron emission tomography in humans to examine the association between cerebral 5-HT(4)Rs and common obesity. We found in humans a strong positive association between body mass index and the 5-HT(4)R density bilaterally in the two reward ‘hot spots’ nucleus accumbens and ventral pallidum, and additionally in the left hippocampal region and orbitofrontal cortex. These findings suggest that the 5-HT(4)R is critically involved in reward circuits that regulate people's food intake. They also suggest that pharmacological stimulation of the cerebral 5-HT(4)R may reduce reward-related overeating in humans.
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, 24 Juliane Maries Vej, DK-2100 Copenhagen, Denmark. haahr@nru.dk
M E
ME
Haahr
P M
PM
Rasmussen
K
K
Madsen
L
L
Marner
C
C
Ratner
N
N
Gillings
W F C
WF
Baaré
G M
GM
Knudsen
D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D049268:Positron-Emission Tomography; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D012201:Reward; D055815:Young Adult
D044422:Receptors, Serotonin, 5-HT4