The effect of naloxone administration on the secretion of corticotropin-releasing hormone, arginine vasopressin, and adrenocorticotropin in unperturbed horses.

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.