The
melanocortin (
ACTH/
MSH)
peptides exert a number of central effects. In the eighties, we described for the first time a role for
melanocortins in the central control of appetite. We showed that the injection of ACTH-(1-24) into a brain lateral ventricle reduced food intake up to 76.6% in starved rats.
Injections into the ventromedial hypothalamus during the nocturnal feeding phase also markedly inhibited food intake. These effects were also confirmed in mice and rabbits. Targeted disruption of the
MC4 receptor resulting in
obesity in mice explained the role of this receptor in mediating effects of
melanocortins on food intake. Administration of
MC4 receptor agonists leads to acute reduction in food intake and
body weight, while the reverse effects are observed after administration of selective
MC4 receptor antagonists, confirming the role of the
melanocortins in mediating a tonic inhibition on feeding behavior. Moreover, immobilization stress-induced
anorexia may be partially reversed by single and repeated intracerebroventricular administration of selective
MC4 receptor antagonists. It is thus evident that
MC4 receptor blockage can reduce stress-induced
anorexia and that repeated
injections of selective
MC4 receptor antagonists have a sustained effect on food intake without any sign of tachyphylaxis. However, we have also shown that the behavioral effects of CRF (
anorexia and grooming) are not influenced by
MC4 receptor blockage. These effects of CRF are thus not due to an indirect mechanism caused by an increased release of
melanocortins acting on the central MC receptors.