title: Peripheral injection of CCK-8S induces Fos expression in the dorsomedial hypothalamic nucleus in rats.
abstract: Peripheral cholecystokinin (CCK) plays a physiological role in the regulation of food intake. The dorsomedial hypothalamic nucleus (DMH) has been implicated in the brain regulation of food intake and satiety. The aim of this study was to determine if peripherally administered CCK affects neuronal activity in the DMH, as assessed by Fos expression. Density of Fos-positive neurons was determined in the DMH, paraventricular nucleus of the hypothalamus (PVN), arcuate nucleus of the hypothalamus (ARC) and ventromedial hypothalamic nucleus (VMH) in non-fasted Sprague-Dawley rats in response to intraperitoneally (ip) injection of CCK-8S (2 microg/kg, n=6) or vehicle (0.15 M NaCl; n=6). CCK-8S increased Fos immunoreactivity in the DMH (mean+/-SEM; cells/section: 108+/-10 versus 54+/-6, p<0.001) and PVN (120+/-12 versus 20+/-3, p<0.001) compared to the vehicle group while not influencing Fos expression in the ARC and VMH. Double labeling showed that 27.4+/-6.4% (n=3) of Fos-positive neurons induced by CCK-8S were positive for corticotropin-releasing factor immunoreactivity, that were mainly localized in the ventral part of the DMH, and encircled in a network of tyrosine-hydroxylase-immunoreactive positive fibers. These data indicate that in addition of the PVN, peripheral CCK increases neuronal activity in the DMH suggesting a possible role in this hypothalamic nucleus in the satiating effect of the peptide.
authors.affiliation: Department of Medicine, Division Hepatology, Gastroenterology, and Endocrinology, Charité, Campus Virchow, Humboldt-Universität zu Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kobelt
authors.forename: Stephan
authors.initials: S
authors.lastname: Paulitsch
authors.forename: Miriam
authors.initials: M
authors.lastname: Goebel
authors.forename: Andreas
authors.initials: A
authors.lastname: Stengel
authors.forename: Marco
authors.initials: M
authors.lastname: Schmidtmann
authors.forename: Ivo R
authors.initials: IR
authors.lastname: van der Voort
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Tebbe
authors.forename: Rüdiger W
authors.initials: RW
authors.lastname: Veh
authors.forename: Burghard F
authors.initials: BF
authors.lastname: Klapp
authors.forename: Bertram
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
authors.forename: Hubert
authors.initials: H
authors.lastname: Mönnikes
mesh_terms: D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects* / Q000502:physiology; D001369:Axons / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D002452:Cell Count; D002766:Cholecystokinin / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: C090019:8-sulfocholecystokinin octapeptide; D000305:Adrenal Cortex Hormones; D002395:Catecholamines; D018697:Nootropic Agents; D016760:Proto-Oncogene Proteins c-fos; D000324:Adrenocorticotropic Hormone; D002766:Cholecystokinin; D003346:Corticotropin-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase; D012844:Sincalide