title: Peripheral injected cholecystokinin-8S modulates the concentration of serotonin in nerve fibers of the rat brainstem.
abstract: Serotonin and cholecystokinin (CCK) play a role in the short-term inhibition of food intake. It is known that peripheral injection of CCK increases c-Fos-immunoreactivity (Fos-IR) in the nucleus of the solitary tract (NTS) in rats, and injection of the serotonin antagonist ondansetron decreases the number of c-Fos-IR cells in the NTS. This supports the idea of serotonin contributing to the effects of CCK. The aim of the present study was to elucidate whether peripherally injected CCK-8S modulates the concentration of serotonin in brain feeding-regulatory nuclei. Ad libitum fed male Sprague-Dawley rats received 5.2 and 8.7 nmol/kg CCK-8S (n=3/group) or 0.15M NaCl (n=3-5/group) injected intraperitoneally (ip). The number of c-Fos-IR neurons, and the fluorescence intensity of serotonin in nerve fibers were assessed in the paraventricular nucleus (PVN), arcuate nucleus (ARC), NTS and dorsal motor nucleus of the vagus (DMV). CCK-8S increased the number of c-Fos-ir neurons in the NTS (mean±SEM: 72±4, and 112±5 neurons/section, respectively) compared to vehicle-treated rats (7±2 neurons/section, P<0.05), but did not modulate c-Fos expression in the DMV or ARC. Additionally, CCK-8S dose-dependently increased the number of c-Fos-positive neurons in the PVN (218±15 and 128±14, respectively vs. 19±5, P<0.05). In the NTS and DMV we observed a decrease of serotonin-immunoreactivity 90 min after injection of CCK-8S (46±2 and 49±8 pixel/section, respectively) compared to vehicle (81±8 pixel/section, P<0.05). No changes of serotonin-immunoreactivity were observed in the PVN and ARC. Our results suggest that serotonin is involved in the mediation of CCK-8's effects in the brainstem.
authors.affiliation: Medical Clinic, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Kim-Marie
authors.initials: KM
authors.lastname: Engster
authors.affiliation: Medical Clinic, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Frommelt
authors.affiliation: Medical Clinic, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hofmann
authors.affiliation: Medical Clinic, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Nolte
authors.affiliation: Medical Clinic, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Fischer
authors.affiliation: Medical Clinic, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Rose
authors.affiliation: Medical Clinic, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stengel
authors.affiliation: Medical Clinic, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Germany. Electronic address: peter.kobelt@charite.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Kobelt
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism*; D002766:Cholecystokinin / Q000008:administration & dosage* / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects* / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; C410885:cholecystokinin 8; D012701:Serotonin; D002766:Cholecystokinin
keywords: C-Fos; Cholecystokinin; Dorsal motor nucleus of the vagus; Nucleus of the solitary tract; Paraventricular nucleus of the hypothalamus; Serotonin