Plasma hormone levels and central c-Fos expression in ferrets after systemic administration of cholecystokinin.
Posterior pituitary hormone secretion and central neural expression of the immediate-early gene product c-Fos was examined in adult ferrets after intravenous administration of CCK octapeptide. Pharmacological doses of CCK (1, 5, 10, or 50 microg/kg) did not induce emesis, but elicited behavioral signs of nausea and dose-related increases in plasma vasopressin (AVP) levels without significant increases in plasma oxytocin (OT) levels. CCK activated neuronal c-Fos expression in several brain stem viscerosensory regions, including a dose-related activation of neurons in the dorsal vagal complex (DVC). Activated brain stem neurons included catecholaminergic and glucagon-like peptide-1-positive cells in the DVC and ventrolateral medulla. In the forebrain, activated neurons were prevalent in the paraventricular and supraoptic nuclei of the hypothalamus and also were observed in the central nucleus of the amygdala and bed nucleus of the stria terminalis. Activated hypothalamic neurons included cells that were immunoreactive for AVP, OT, and corticotropin-releasing factor. Comparable patterns of brain stem and forebrain c-Fos activation were observed in ferrets after intraperitoneal injection of lithium chloride (LiCl; 86 mg/kg), a classic emetic agent. However, LiCl activated more neurons in the area postrema and fewer neurons in the nucleus of the solitary tract compared with CCK. Together with results from previous studies in rodents, our findings support the view that nauseogenic treatments activate similar central neural circuits in emetic and nonemetic species, despite differences in treatment-induced emesis and pituitary hormone secretion.
Billig
I
I
Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. ibillig@pitt.edu
Yates
B J
BJ
Rinaman
L
L
D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D001522:Behavior, Animal / Q000187:drug effects; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002452:Cell Count; D002766:Cholecystokinin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005289:Ferrets; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D018021:Lithium Chloride / Q000008:administration & dosage; D008297:Male; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D010121:Oxytocin / Q000097:blood; D010446:Peptide Fragments / Q000378:metabolism; D010909:Pituitary Hormones, Posterior / Q000097:blood*; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D014839:Vomiting / Q000139:chemically induced / Q000503:physiopathology
D010446:Peptide Fragments; D010909:Pituitary Hormones, Posterior; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D001127:Arginine Vasopressin; D010121:Oxytocin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002766:Cholecystokinin; D018021:Lithium Chloride