Evidence for an interaction between neuropeptide Y and the melanocortin-4 receptor on feeding in the rat

The hypothalamus is a critical centre for the control of appetite. Neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (alpha-MSH) exert opposing effects on feeding and substantial neuroanatomical evidence exists to suggest these hypothalamic peptides may interact to alter feeding behaviour. We have examined central interactions between these two peptide systems on food intake in satiated male Sprague-Dawley rats. NPY-induced (1 nmol; i.c.v.) food intake was significantly attenuated by subsequent alpha-MSH administration (1 and 4 nmol; i.c.v.) at 1 h post-injection and persisted for the entire 4 h observation period (P<0.05). Central administration of the selective MC4-R antagonist HS014 (0.5 nmol) significantly increased food intake compared to saline-vehicle (P<0.05). However, co-administration of HS014 (0.5 nmol) and NPY (0.5 and 1 nmol) did not increase feeding compared to either dose of NPY alone. These results taken together provide some evidence for an interaction between these mediators in the control of food intake.