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.) inj ections of ACTH(1-24) (1 mu g) induced a display of excessive grooming , and increased the plasma concentrations of ACTH and corticosterone. Pituitary-adrenal activation was blocked by pretreatment with dexameth asone, 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 mu g of a non-selective melanocortin-3/4-receptor antagonist (S HU 9119), or of 5 and 10 mu g of a selective melanocortin-4-receptor a ntagonist ([D-Arg(8)]ACTH(4-10)), coadministered (i.c.v.) with 1 mu g ACTH(1-24), inhibited the ACTH(1-24)-induced activation of the hypotha lamus-pituitary-adrenal-axis and excessive grooming. 3 In addition, se veral doses of the selective melanocortin-3-receptor agonist Lys-gamma (2)-MSH were centrally administered, but neither neuroendocrine, nor e xcessive grooming responses were observed. 4 These results imply that the melanocortin-4-receptor, and not the melanocortin-3-receptor, is i nvolved in the ACTH(1-24)-induced rise in plasma levels of ACTH and co rticosterone, and excessive grooming.