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 mug/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.