INFLUENCE OF OPIOID-PEPTIDES ON RELEASE FROM VASOPRESSIN AND OXYTOCIN NEURONS OF THE HYPOTHALAMONEUROHYPOPHYSEAL SYSTEM - EFFECTS OF NALOXONE IN THE CONSCIOUS RAT

We examined the effects of acute and chronic treatments with naloxone on release of vasopressin and oxytocin from the hypothalamoneurohypophyseal system (HNS) in conscious, chronically instrumented Long-Evans rats. Plasma concentrations of vasopressin-associated neurophysin and oxytocin-associated neurophysin were evaluated before and during an intravenous infusion of 18% saline at 100 μL · kg-1 body weight · min-1 for 60 min. Acute treatment with naloxone (2.75 μmol/kg, intravenous) did not measurably alter basal plasma osmolality or vasopressin-associated neurophysin concentration, but it caused a three-fold rise in basal plasma oxytocin-associated neurophysin concentration (16 ± 2 to 46 ± 3 fmol/mL, p < 0.005). Chronic treatment with naloxone (13.75 μmol/day, subcutaneous pellets) increased plasma osmolality (292 ± 1 to 300 ± 2 mosmol/kg H2O, p < 0.01) by day 5, but it had no measurable effects on basal vasopressin- or oxytocin-associated neurophysin concentration. There were also no significant differences in plasma sodium concentration (144.8 ± 1.1 vs. 142.2 ± 1.4 mequiv./L) under both conditions. Acute and chronic treatments with naloxone accompanied by salt loading produced a five- and four-fold decrease in the rates that plasma concentration of vasopressin-associated neurophysin changed with plasma osmolality, compared with untreated salt-loaded control rats. For oxytocin secretion from the HNS, both treatments accompanied by salt loading substantially decreased the threshold for changes in relation to plasma osmolality; the rise in plasma concentration of oxytocin-associated neurophysin was similar at all levels of hyperosmotic stimulation. A strongly correlated relationship between plasma oxytocin-associated neurophysin and plasma osmolality (r = 0.739) found for control animals became poorly correlated following treatments (acute, r = 0.173; chronic r = -0.079). Our results suggest that in conscious rats, endogenous opioid peptides enhance the secretion of vasopressin from neurones of the HNS in response to hyperosmotic stimulation but inhibit both basal and stimulated release of oxytocin.