Stress-induced hypokinesia is facilitated by ACTH-(7-10).
Subcutaneous treatment with the neuropeptide ACTH-(4-10) induced hypokinesia in rats subjected to a mild stress induced by placing the animals on a non-functional "hot" plate (21 degrees C) for 30 sec, but not in control animals not exposed to this stress-inducing environment. The lowest effective dose of ACTH-(4-10) was 5 micrograms/kg, administered 50 min before testing. The combination of peptide treatment and the mild stress-inducing procedure mimicked the effect of a short intense stress induced by placing the rats on a hot plate (57 degrees C) for 30 sec, suggesting that this stress-induced hypokinesia is mediated by ACTH neuropeptides. Structure-activity relationship studies revealed that the active core for the ACTH-(4-10)-induced hypokinesia is located in the C-terminal tetrapeptide Phe-Arg-Try-Gly (ACTH-(7-10)). Pretreatment with the opioid antagonist naltrexone did not influence the effect of ACTH-(4-10) indicating that activation of opioid systems is not implicated in this behavioral effect of the peptide.
Wolterink
G
G
Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.
Van Ree
J M
JM
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009271:Naltrexone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013315:Stress, Psychological / Q000503:physiopathology*; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; C042086:ACTH (7-10); D009271:Naltrexone; D000324:Adrenocorticotropic Hormone