Mu Opioid Modulation of Oxytocin Secretion in Late Pregnant and Parturient Rats

Abstract

We have investigated effects of µ- and ĸ-opioid agonists and antagonists on plasma oxytocin levels and noradrenaline content in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of 20-day pregnant rats. β-Endorphin, oxytocin, estrogen and progesterone profiles in late pregnant and parturient rats were also sought. Stage of estrous cycle was monitored by vaginal smear, and pro-estrous animals were left overnight with male. In the first set of experiments, pregnant rats were monitored and decapitated on days 20 and 21 and after the delivery of second pup. In the second set, 20-day pregnant rats were intracerebroventricularly infused with morphine (50 µg/10 µl), U50,488H (ĸ-agonist; 50 µg/10 µl), clocinnamox (µ-antagonist; 50 µg/10 µl) and norbinaltorphimine (ĸ-antagonist; 50 µg/10 µl). Controls received saline alone. Serum estrogen and progesterone levels were measured by enzyme immunoassay, and plasma oxytocin and β-endorphin by radioimmunoassay. Noradrenaline and its metabolite (3,4-dihydroxyphenylglycol) were determined in micropunched hypothalamic nuclei by HPLC-ECD. In parturient rats, oxytocin levels were increased (p < 0.05) and β-endorphin decreased (p < 0.01) compared to 20-day pregnant animals. Serum progesterone concentrations progressively declined towards parturition (p < 0.001). Clocinnamox raised oxytocin levels (p < 0.01) while U50,488H caused decreases (p < 0.05). Noradrenaline content was elevated by clocinnamox in the SON (p < 0.01) and PVN (p < 0.05) compared to control values. Other agonists and antagonists had no significant effect on the noradrenergic neurotransmission or oxytocin secretion. We suggest that noradrenaline may mediate the inhibitory effects of µ-opioids on oxytocin release. Our findings have also shown that ĸ-opioid receptors are not involved in modulation of oxytocin neurons in late pregnant rats.

Coexpression of the mu‐opioid receptor splice variant MOR1C and the vesicular glutamate transporter 2 (VGLUT2) in rat central nervous system

“…It has been reported that hypophysiotropic peptides such as thyrotropin-releasing hormone, gonadotropin-releasing hormone, corticotrophin-releasing hormone, and somatostatin are coexpressed with VGLUT2 (Hrabovszky et al, Hrabovszky et al, 2005a,b, 2006. Thus, our data suggest that activation of MOR 1C may modulate the release of some hypophysiotropic hormones (Plotsky, 1986;Doi et al, 2001;Kutlu et al, 2004).…”

Dopaminergic Mechanisms Involved in Prolactin Release after Mifepristone and Naloxone Treatment during Late Pregnancy in the Rat

“…We hypothesize that oxytocin may be a good candidate. In vivo and in vitro studies have demonstrated that oxytocin is a potential prolactin-releasing factor [59, 60] Although it was suggested that oxytocin is not involved in the control of prolactin secretion at this time [57] because the antepartum prolactin surge was not inhibited by infusion of a specific oxytocin antagonist, we cannot rule out existing evidence that could support our hypothesis [61,62,63]. …”

Neurotransmitters Involved in the Opioid Regulation of Prolactin Secretion at the End of Pregnancy in Rats

“…When we studied the effect of the combined treatment of DAMGO with serotoninergic or GABAergic antagonists, a single time point was examined. Although our study suggests the participation of these neurotransmitters in the stimulation of prolactin release 30 min after DAMGO administration, we cannot exclude the possibility that other responses may have occurred at earlier or later time points, as for instance an indirect effect of (mu)receptor-mediated modulation of oxytocin secretion [78]. …”