title: Gastric distension enhances CCK-induced Fos-like immunoreactivity in the dorsal hindbrain by activating 5-HT3 receptors.
abstract: The combination of gastric distension and cholecystokinin (CCK) enhances both suppression of food intake and induction of c-Fos-like immunoreactivity (Fos-LI) in the dorsal vagal complex (DVC). Previously, we have shown that serotonin type-3 (5-HT3) receptor mediation of suppression of food intake by CCK requires gastric participation. Therefore, we hypothesized that 5-HT3 receptors mediate CCK-induced Fos-LI in the dorsal hindbrain through a mechanism that involves gastric distension. To test this hypothesis, we counted Fos-LI in the DVC of ondansetron (1 mg/kg; 5-HT3 receptor antagonist) and vehicle-treated rats following gastric balloon distension (5 ml), CCK (1 microg/kg) administration, or CCK combined with gastric distension. Ondansetron administration attenuated DVC Fos-LI by CCK administration. Likewise, ondansetron attenuated Fos-LI by gastric distension in the DVC, specifically within the nucleus of the solitary tract (NTS) and area postrema (AP) nuclei. The most pronounced attenuation of distension-induced Fos-LI by ondansetron occurred in the NTS, particularly in the medial and intermedial NTS. When combined, CCK and gastric distension enhanced Fos-LI in the DVC greater than each treatment alone. Furthermore, ondansetron administration attenuated the overall DVC enhanced Fos-LI induced by CCK + gastric distension, in particular at the NTS and AP nuclei. We found that, within the mid-to-caudal regions of the NTS and AP, 5-HT3 receptors most significantly mediate neuronal activation by CCK + distension. In conjunction with previous behavioral data, these results show that gastric distension enhances CCK-induced neuronal activation in the DVC by activating 5-HT3 receptors.
authors.affiliation: Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, 126 South Henderson, University Park, PA 16802-6504, USA. mrh212@psu.edu
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hayes
authors.forename: Mihai
authors.initials: M
authors.lastname: Covasa
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology*; D004347:Drug Interactions; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D016761:Oncogene Proteins v-fos / Q000378:metabolism*; D017294:Ondansetron / Q000494:pharmacology; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology*; D012249:Rhombencephalon / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects / Q000294:innervation / Q000502:physiology
chemical_list: D002756:Cholagogues and Choleretics; D016761:Oncogene Proteins v-fos; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017294:Ondansetron; D002766:Cholecystokinin