Naloxone Effects on Plasma Vasopressin and Oxytocin Concentrations Elevated by Histamine, Nicotine, Isoproterenol and an Acute Increase in [NaCl] in Cerebrospinal Fluid

Abstract

Endogenous opioid peptides inhibit secretion of oxytocin during dehydration, hemorrhage and parturition and attenuate release of vasopressin by tail electroshock. Diverse agents were used to stimulate the hypothalamo-neurohypophysial system to investigate the hypothesis that if oxytocin (or vasopressin) release were inhibited by opioid peptides regardless of the stimulus, the site of opiate action may be in the final common pathway (i.e. the magnocellular neuron) or on pituicytes in the neural lobe. Using male Sprague-Dawley rats, we therefore investigated the effect of an opiate receptor antagonist, naloxone (5 mg/kg s.c), on the plasma concentrations of oxytocin and vasopressin elevated by various pharmacologic stimuli, including histamine (10 mg/kg i.p.), nicotine (0.15 or 1.5 mg/kg i.p.), isoproterenol (30 or 120 ug/kg i.m.) and increased [NaCl] in cerebrospinal fluid (CSF; 10 µl artificial CSF containing 1 MNaCl i.v.t.). Control animals received saline (0.85%) or artificial CSF (containing 0.16 M NaCl). Animals were decapitated 60 s (†[NaCΓJ in CSF) or 10 min after the stimulus or vehicle. Vasopressin and oxytocin were extracted from plasma and quantified by RIA. The concentrations of oxytocin and vasopressin in plasma were elevated (p < 0.05) by histamine, isoproterenol (30 and 120 αg/ kg), ↑[NaCl] in CSF, and nicotine at the higher (1.5 mg/kg) but not lower (0.15 mg/kg) dose. Naloxone increased further (p<0.05) the concentration of oxytocin in plasma after histamine, nicotine (0.15 and 1.5 mg/kg), isoproterenol (30 and 120 µg/kg) and ↑[NaCl] in CSF. Naloxone also increased (p<0.05) oxytocin concentration in controls receiving CSF or saline. Vasopressin concentration was unaffected by naloxone in either controls or after any of the stimuli. We conclude that endogenous opioid peptides inhibit release of oxytocin in vivo by an effect on the final common pathway, i.e. the magnocellular neuron or on pituicytes in the neural lobe.

Naloxone Potentiation of Effects of Cholecystokinin and Lithium Chloride on Oxytocin Secretion, Gastric Motility and Feeding

“…Potentiation of neurohypophyseal OT secretion in rats by the opioid antagonist naloxone is known to occur in re sponse to cellular dehydration, hypovolemia, parturition, restraint, and perhaps suckling [3,8,15,16,20,21]. Our re sults now indicate that the elevation of plasma OT levels produced by systemic injection of CCK and LiCI similarly is potentiated by naloxone.…”

Opioid tolerance and dependence in the magnocellular oxytocin system: a physiological mechanism?

“…In non-pregnant, conscious rats, naloxone has no effect upon the basal plasma concentration of oxytocin, indicating little or no endogenous opioid restraint of basal secretion. In contrast, from about day 10 of pregnancy until term (day 21), naloxone injections elevate oxytocin release, most markedly at term, reflecting active restraint of secretion by endogenous opioids (Hartman et al 1986;Douglas et al 1993b). …”

Central Oxytocin Mediates Inhibition of Sodium Appetite by Naloxone in Hypovolemic Rats

“…A growing body of evidence suggests that at least one aspect of OT regulation is sub served by endogenous opioid pathways [9,10], Opioid peptides are localized within magnocellular OT-synthesizing neurons [11,12], and opiate receptors have been demonstrated both in the neural lobe of the pituitary [13,14] and in the supraoptic and paraventricular nuclei of the hypothalamus [15]. Treatment with opioid antago nists such as naloxone results in a pronounced increase in the spontaneous firing activity of OT neurons and en hanced pituitary release of OT in response to a variety of stimuli, both in vivo and in vitro [16][17][18][19], Such studies have indicated that both the cell bodies and nerve termi nals of OT neurons are potential sites at which endoge nous opioid peptides may inhibit OT release.…”