Dorsal hindbrain 5-HT3 receptors participate in control of meal size and mediate CCK-induced satiation.
We have previously shown that systemic administration of ondansetron, a selective serotonin type-3 (5-HT3) receptor antagonist, attenuates cholecystokinin (CCK)-induced suppression of food intake. The exact location of 5-HT3 receptors mediating this action is not clear and may involve hindbrain 5-HT3 receptors. In this study, we first examined sucrose intake in response to direct injections of ondansetron into various sites of the dorsal hindbrain. Ondansetron (1.0 and 2.0 microg/100 nl) delivered into the medial nucleus of the solitary tract (NTS) significantly increased 15% sucrose intake (12.2 +/- 0.6 and 13.5 +/- 0.7 ml, respectively) compared to control (10.2 +/- 0.7 ml), while equivalent injections into ipsilateral adjacent sites such as the lateral NTS, dorsal medial nucleus of the vagus, and other areas of the dorsal hindbrain had no effect on sucrose intake. Second, we examined the effects of hindbrain 5-HT3 receptor blockade on suppression of intake by systemic CCK. Fourth ventricular (i.c.v.) administration of ondansetron (10.0 microg/3.0 microl) significantly attenuated suppression of intake by CCK (9.1 +/- 1.0 vs. 6.4 +/- 0.4 ml, respectively). Ondansetron alone had no effect on sucrose intake at any i.c.v. dose tested. In a separate group of rats, CCK administration suppressed 60-min intake significantly (8.9 +/- 0.8 ml) compared to control (12.4 +/- 0.4 ml). Administration of ondansetron into the medial NTS completely reversed suppression of intake by CCK (11.8 +/- 1.0 and 12.3 +/- 1.4 ml, for 0.5 microg and 1.0 microg/100 nl, respectively). These data demonstrate that 5-HT3 receptors located in the medial NTS participate in control of meal size and mediate CCK-induced suppression of food intake.
Hayes
Matthew R
MR
Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, 126 South Henderson, University Park, PA 16802, USA.
Covasa
Mihai
M
D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D017294:Ondansetron / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000502:physiology*; D012249:Rhombencephalon / Q000502:physiology*; D012528:Satiety Response / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017552:Solitary Nucleus / Q000187:drug effects; D013395:Sucrose
D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017294:Ondansetron; D013395:Sucrose; D002766:Cholecystokinin