The role of central melanocortin receptors in the activation of the hypothalamus-pituitary-adrenal-axis and the induction of excessive grooming.

1. In accord with previous studies intracerebroventricular (i.c.v.) injections of ACTH1-24 (1 microg) induced a display of excessive grooming, and increased the plasma concentrations of ACTH and corticosterone. Pituitary-adrenal activation was blocked by pretreatment with dexamethasone, indicating that the effect of the (i.c.v.) injected peptide was not caused by a peripheral effect on the adrenal cortex. 2. Doses of 1 and 3 microg of a non-selective melanocortin-3/4-receptor antagonist (SHU 9119), or of 5 and 10 microg of a selective melanocortin-4-receptor antagonist ([D-Arg8]ACTH4-10), coadministered (i.c.v.) with 1 microg ACTH1-24, inhibited the ACTH1-24-induced activation of the hypothalamus-pituitary-adrenal-axis and excessive grooming. 3. In addition, several doses of the selective melanocortin-3-receptor agonist Lys-gamma2-MSH were centrally administered, but neither neuroendocrine, nor excessive grooming responses were observed. 4. These results imply that the melanocortin-4-receptor, and not the melanocortin-3-receptor, is involved in the ACTH1-24-induced rise in plasma levels of ACTH and corticosterone, and excessive grooming.