Peripheral injection of CCK-8S induces Fos expression in the dorsomedial hypothalamic nucleus in rats.
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.
Kobelt
Peter
P
Department of Medicine, Division Hepatology, Gastroenterology, and Endocrinology, Charité, Campus Virchow, Humboldt-Universität zu Berlin, Germany.
Paulitsch
Stephan
S
Goebel
Miriam
M
Stengel
Andreas
A
Schmidtmann
Marco
M
van der Voort
Ivo R
IR
Tebbe
Johannes J
JJ
Veh
Rüdiger W
RW
Klapp
Burghard F
BF
Wiedenmann
Bertram
B
Taché
Yvette
Y
Mönnikes
Hubert
H
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
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