5-HT3 receptors participate in CCK-induced suppression of food intake by delaying gastric emptying

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 287; no. 4; pp. R817 - R823
• Main Authors: Hayes, Matthew R, Moore, Rachael L, Shah, Samit M, Covasa, Mihai
• Format: Journal Article
• Language: English
• Published: United States 01.10.2004
• Subjects: Animals; Appetite Depressants; Cholecystokinin - pharmacology; Eating - drug effects; Feedback - drug effects; Feedback - physiology; Gastric Emptying - drug effects; Gastric Emptying - physiology; Glucose - pharmacology; Male; Ondansetron - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Serotonin, 5-HT3 - drug effects; Receptors, Serotonin, 5-HT3 - physiology; Satiety Response - drug effects; Serotonin Antagonists - pharmacology
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00295.2004

Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, Pennsylvania 16802-6504 Submitted 4 May 2004 ; accepted in final form 2 June 2004 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. ondansetron; serotonin; osmotic; glucose; satiety Address for reprint requests and other correspondence: M. R. Hayes, Dept. of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State Univ., 126 South Henderson, University Park, PA 16802