title: The effect of naloxone administration on the secretion of corticotropin-releasing hormone, arginine vasopressin, and adrenocorticotropin in unperturbed horses.
abstract: We used our nonsurgical method for collecting equine pituitary venous blood to study the role of endogenous opioids in the basal regulation of the hypothalamo-pituitary-adrenal axis. We gave mares the opioid antagonist, naloxone (NAL), at either a high (0.5 mg/kg i.v. bolus, followed by infusion of 0.25 mg/kg.h; n = 4) or low (0.2 mg/kg i.v. bolus; n = 6) dose rate. Pituitary venous blood was collected continuously, divided into 0.5- or 1-min segments for 15-30 min before and 1 h after the NAL bolus, and assayed for CRH, arginine vasopressin (AVP), and ACTH. The mares tolerated NAL administration well, with little difference between dose rates in the mild transient side-effects. Both NAL doses increased jugular cortisol concentrations (high, P = 0.0022; low, P = 0.0001) and the ACTH secretion rate (high, P = 0.0056; low, P = 0.0103). High dose NAL raised the secretion rates of AVP (P = 0.0252) and CRH (P = 0.0106); however, the magnitude of ACTH responses exceeded those in AVP and CRH, as shown by increased ratios between ACTH and AVP (P = 0.0246) or CRH (P = 0.0122) secretion rates. After low dose NAL, neither CRH nor AVP secretion was altered. Indeed, CRH declined as ACTH rose in 4 mares and was unchanged in a fifth mare. When data from the 10 mares were pooled, mean secretion rates of ACTH and CRH were correlated after (P < 0.05), but not before, NAL treatment. Overall, mean ACTH and AVP secretion rates were not correlated during any 30-min period, but in individual mares, minute to minute AVP and ACTH secretion patterns were always correlated. We conclude that endogenous opioids inhibit the equine hypothalamo-pituitary-adrenal axis under basal conditions; however, their sites of action do not appear to lie solely on CRH and/or AVP neurons. It seems likely that endogenous opioids also inhibit the release of a third ACTH secretagogue or promote the secretion of an ACTH release inhibitory factor.
authors.affiliation: Department of Endocrinology, Christchurch Public Hospital, New Zealand.
authors.forename: S L
authors.initials: SL
authors.lastname: Alexander
authors.forename: C H
authors.initials: CH
authors.lastname: Irvine
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006736:Horses / Q000502:physiology*; D006854:Hydrocortisone / Q000097:blood; D007700:Kinetics; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D010902:Pituitary Gland / Q000098:blood supply; D014680:Veins
chemical_list: D001127:Arginine Vasopressin; D009270:Naloxone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone