Selective melanocortin MC4 receptor blockage reduces immobilization stress-induced anorexia in rats

We investigated the effects of selective melanocortin MC4 receptor blockage on immobilization stress-induced anorexia. Male rats were subjected to imm obilization once a day for 4 days. Prior to each of the stress treatments, the rats were injected i.c.v. (intracerebroventricularly) with either salin e or the melanocortin MC4 receptor antagonist HS014 (cyclic [AcCys(11), D-N al(14), Cys(18) Asp-NH222]beta-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 i n the stressed group treated with HS014 was significantly higher than in th e stressed group and significantly lower than in the control group. Repeate d injections of the melanocoain MC4 receptor antagonist were effective and there were no signs of tachyphylaxis. This is the first report showing that melanocortin MC4 receptor blockage can relieve an anorectic condition, whi ch may indicate that melanocortin MC4 receptor blockage is an effective way to treat anorectic disorders. (C) 1999 Elsevier Science B.V. All rights re served.