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

In accord with previous studies intracerebroventricular (i.c.v.) injections of ACTH1-24 (1 g) 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. Doses of 1 and 3 g of a non-selective melanocortin-3/4-receptor antagonist (SHU 9119), or of 5 and 10 g of a selective melanocortin-4-receptor antagonist ([D-Arg8]ACTH4-10), coadministered (i.c.v.) with 1 g ACTH1-24, inhibited the ACTH1-24-induced activation of the hypothalamus-pituitary-adrenal-axis and excessive grooming. In addition, several doses of the selective melanocortin-3-receptor agonist Lys-2-MSH were centrally administered, but neither neuroendocrine, nor excessive grooming responses were observed. 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