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.
Von Frijtag
J C
JC
Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Utrecht University, The Netherlands.
Croiset
G
G
Gispen
W H
WH
Adan
R A
RA
Wiegant
V M
VM
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000595:Amino Acid Sequence; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003366:Cosyntropin / Q000008:administration & dosage / Q000494:pharmacology; D006120:Grooming / Q000187:drug effects / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D008969:Molecular Sequence Data; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D044101:Receptors, Melanocortin
D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C103272:SHU 9119; D003366:Cosyntropin; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; D003345:Corticosterone