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

Abstract

1. In accord with previous studies intracerebroventricular (i.c.v.) injections of ACTH_1-24 (1 μg) 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 μg of a non-selective melanocortin-3/4-receptor antagonist (SHU 9119), or of 5 and 10 μg of a selective melanocortin-4-receptor antagonist ([D-Arg⁸]ACTH_4-10), coadministered (i.c.v.) with 1 μg ACTH_1-24, inhibited the ACTH_1-24-induced activation of the hypothalamus-pituitary-adrenal-axis and excessive grooming.

3. In addition, several doses of the selective melanocortin-3-receptor agonist Lys-γ₂-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 ACTH_1-24-induced rise in plasma levels of ACTH and corticosterone, and excessive grooming.

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