5-HT3 receptors participate in CCK-induced suppression of food intake by delaying gastric emptying.
Serotonin type 3 (5-HT(3)) receptors have been shown to participate in the negative-feedback control of food intake. We previously reported that cholecystokinin (CCK)-induced suppression of food intake is partly mediated through 5-HT(3) receptors when rats were tested on a preferred liquid diet, but whether such an effect occurs when they are tested on a solid maintenance diet is unknown. In the present study, we examined the effects of ondansetron, a selective 5-HT(3) antagonist, on CCK-induced suppression of solid chow intake. Intraperitoneal administration of ondansetron significantly attenuated 30- and 60-min CCK-induced reduction of food intake, with suppression being completely reversed by 120 min. It is not known whether 5-HT(3) receptors directly mediate CCK-induced satiation or whether their participation depends on CCK acting as part of a feedback cascade to inhibit ongoing intake. Because CCK-induced inhibition of sham feeding does not depend on additive gastric/postgastric-feedback signals, we examined the ability of ondansetron to reverse CCK-induced satiation in sham-feeding rats. Ondansetron did not attenuate reduction of sham feeding by CCK, suggesting that ondansetron does not directly antagonize CCK-satiation signals. CCK suppresses real feeding through a delay in gastric emptying. Ondansetron could attenuate CCK-induced reduction of food intake by reversing CCK-induced inhibition of gastric emptying. We found that blockade of 5-HT(3) receptors attenuates CCK-induced inhibition of gastric emptying of a solid meal, as well as saline and glucose loads. We conclude that 5-HT(3) receptors mediate CCK-induced satiation through indirect mechanisms as part of a feedback cascade involving inhibition of gastric emptying.
Hayes
Matthew R
MR
Dept. of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State Univ., 126 South Henderson, University Park, PA 16802, USA.
Moore
Rachael L
RL
Shah
Samit M
SM
Covasa
Mihai
M
D000818:Animals; D001067:Appetite Depressants; D002766:Cholecystokinin / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D005246:Feedback / Q000187:drug effects / Q000502:physiology; D005746:Gastric Emptying / Q000187:drug effects* / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000502:physiology*; D012528:Satiety Response / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology
D001067:Appetite Depressants; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017294:Ondansetron; D002766:Cholecystokinin; D005947:Glucose