Selective melanocortin MC 4 receptor blockage reduces immobilization stress-induced anorexia in rats

Abstract

We investigated the effects of selective melanocortin MC 4 receptor blockage on immobilization stress-induced anorexia. Male rats were subjected to immobilization once a day for 4 days. Prior to each of the stress treatments, the rats were injected i.c.v. (intracerebroventricularly) with either saline or the melanocortin MC 4 receptor antagonist HS014 (cyclic [AcCys 11, d-Nal 14, Cys 18, Asp-NH 2 22]β-MSH-(11–22) (melanocyte-stimulating hormone). Rats subjected to neither stress nor i.c.v. injections served as controls. The results showed that the cumulative food intake and body weight gain in the stressed group treated with HS014 was significantly higher than in the stressed group and significantly lower than in the control group. Repeated injections of the melanocortin MC 4 receptor antagonist were effective and there were no signs of tachyphylaxis. This is the first report showing that melanocortin MC 4 receptor blockage can relieve an anorectic condition, which may indicate that melanocortin MC 4 receptor blockage is an effective way to treat anorectic disorders.