Chronic melanocortin 4 receptor blockage causes obesity without influencing sexual behavior in male rats.

We investigated the effects of continuous intracerebroventricular infusion of a melanocortin 4 receptor antagonist HS014 (cyclic [AcCys11, D-Nal14, Cys18, Asp-NH2(22)]beta-MSH-(11-22)) over 12 days and a subsequent 12-day recovery period on food intake, body weight and copulatory behavior in male rats. The results show that the food intake increased immediately after the start of the infusion of HS014 (0.16 nmol/h) and progressively increased thereafter. No tachyphylaxis was observed. When the infusion of HS014 was terminated, the food-intake levels dropped. The body weights of the rats had increased by 17% by the end of the study, compared with controls. During the recovery period, the body weight decreased towards the levels of the control rats. These results indicate that overeating and the subsequent increases in body weight caused by blockage of the melanocortin 4 (MC4) receptor are reversible when the blockage is ended. We also tested the copulatory behavior of vigorous male rats in the presence of female rats in estrous. We registered mount latency, the number of mounts, the intromission latency, the number of intromissions, the ejaculation latency and the post-ejaculatory interval three times during the study and also after acute administration of HS014 and alpha-MSH. The sexual behavior of the male rats was not affected. These results indicate that the MC receptors, in particular the MC4 receptor, may not be a major mediator of effects on copulatory behavior in male rats.