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.