Cholecystokinin and D-fenfluramine inhibit food intake in oxytocin-deficient mice.
Results from previous studies indicate that oxytocin (OT)-containing neural pathways are activated in laboratory rats after systemic administration of CCK or d-fenfluramine and that centrally released OT may participate in the anorexigenic effects of these treatments. To explore the relationship between feeding behavior and OT function, the effects of CCK and d-fenfluramine on feeding and central c-Fos expression were compared in wild-type (OT+/+) and OT-deficient mice (OT-/-) of C57BL/6 background. Male OT+/+ and OT-/- mice were administered saline or CCK (1, 3, or 10 microg/kg ip) after overnight food deprivation. Saline-treated OT+/+ and OT-/- mice consumed equivalent amounts of food after an overnight fast. CCK inhibited deprivation-induced food intake in a dose-dependent manner to a similar extent in both genotypes. CCK treatment also induced similar hindbrain and forebrain patterns of increased c-Fos expression in mice of both genotypes. After treatment with d-fenfluramine (10 mg/kg ip), both OT+/+ and OT-/- mice consumed significantly less food than untreated controls, with no difference between genotypes. We conclude that OT signaling pathways are unnecessary for the anorexigenic effects of systemically administered CCK and d-fenfluramine in C57BL/6 mice.
Mantella
Rose C
RC
Dept. of Pharmaceutical Sciences, Univ. of Pittsburgh, 904 Salk Hall, Pittsburgh, PA 15261, USA. rcmst22@pitt.edu
Rinaman
Linda
L
Vollmer
Regis R
RR
Amico
Janet A
JA
D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005277:Fenfluramine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005838:Genotype; D007031:Hypothalamus / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010121:Oxytocin / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology
D002766:Cholecystokinin; D005277:Fenfluramine; D010121:Oxytocin; D016760:Proto-Oncogene Proteins c-fos; D017367:Selective Serotonin Reuptake Inhibitors