Lesion of the lateral parabrachial nucleus attenuates the anorectic effect of peripheral amylin and CCK.
Amylin and CCK activate the area postrema (AP)/nucleus of the solitary tract (NTS) - lateral parabrachial nucleus (LPBN) - central amygdala (CeA) pathway. However, except for the brainstem structures the role of these nuclei for the anorectic effect of these peptides is not yet well characterized. The current study investigated the role of the LPBN in mediating the inhibitory effect of peripheral amylin and CCK on feeding behavior. Rats with electrolytic lesions in the LPBN (LPBN-X) were used in behavioral as well as in immunohistological c-Fos studies. LPBN-X significantly reduced the anorectic effect of amylin (5 microg/kg, i.p.). The effect of a higher amylin dose (10 microg/kg, i.p.) was only slightly attenuated in the LPBN-X rats. In agreement with previous studies, LPBN lesions also reduced the inhibitory effect of CCK on food intake. In the immunohistological experiments, amylin and CCK induced c-Fos expression in the AP, NTS, LPBN and CeA in the SHAM rats. Both the amylin- and CCK-induced activation of the CeA was completely abolished in the animals with a LPBN lesion. These results clearly suggest that the signal transduction pathway between the AP/NTS and CeA has been disrupted by the LPBN ablation. We conclude that the LPBN is a crucial brain site mediating the anorectic effect of amylin and CCK. Furthermore, an intact LPBN seems to be essential for the c-Fos response in the CeA induced by these peptides.
Becskei
Csilla
C
Institute of Veterinary Physiology and Centre of Integrative Human Physiology, University of Zurich, 8057 Zurich, Switzerland. csillab@vetphys.uzh.ch
Grabler
Valérie
V
Edwards
Gaylen L
GL
Riediger
Thomas
T
Lutz
Thomas A
TA
D000682:Amyloid; D000704:Analysis of Variance; D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000503:physiopathology; D001522:Behavior, Animal; D001933:Brain Stem / Q000293:injuries* / Q000502:physiology*; D002452:Cell Count; D002766:Cholecystokinin; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D058228:Islet Amyloid Polypeptide; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D016760:Proto-Oncogene Proteins c-fos; D002766:Cholecystokinin