The induction of excessive grooming in the rat by intraventricular application of peptides derived from ACTH: structure-activity studies. |
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| Authors: | W H Gispen V M Wiegant H M Greven D de Wied |
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| Institution: | 1. Division of Molecular Neurobiology, Rudolf Magnus Institute for Pharmacology and the Laboratory of Physiological Chemistry, Medical Faculty, Institute of Molecular Biology, University of Utrecht, Padualaan 8, Utrecht, The Netherlands;2. Scientific Development Group, Organon International BV, Oss, The Netherlands;3. Rudolf Magnus Institute for Pharmacology, University of Utrecht, The Netherlands |
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| Abstract: | Intraventricular administration of synthetic ACTH-like peptides in the rat induces excessive grooming, stretching and yawning. The present study demonstrates that induction of excessive grooming is dose-dependent and independent of the endocrine system. Structure-activity studies show that ACTH1–24, ACTH1–16-NH2, ACTH1–16, α-MSH and βp-MSH are equipotent. Although the presence of the sequence ACTH5–10 in the peptides studies seems of importance in the induction of excessive grooming, it appeared that C-terminal elongation is necessary for the expression of the activity. Administration of D-Phe7] ACTH4–10 and D-Phe7] ACTH1–10 results in appreciable grooming activity of the rat. However, substitution of a D-arginine at the 8 position did not alter the activity of ACTH4–10. The structure-activity relationship of these peptides on grooming activity of the rat is compared to that known for retardation of avoidance extinction. Although some similarities exist, it is concluded that the expression of excessive grooming and retardation of avoidance activity is mediated through different mechanisms. |
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