Central opioids: a possible role in parturition?

Abstract

Pregnant rats were implanted with subcutaneous minipumps to deliver either naloxone or saline. The time-course of subsequent parturition was different between the two groups: the interval between successive births was significantly shorter for the naloxone-treated rats. This supports the hypothesis that the opioid innervation of the neurohypophysis, which is known to influence oxytocin release profoundly, has a physiological role in parturition. To test the further hypothesis that this role is particularly important in a stressful environment, pregnant rats, again implanted with minipumps, were regularly transferred, at 15-min intervals beginning with the birth of the first pup, between their normal cage and the unfamiliar environment of a glass observation chamber. No difference was noted between the time-courses of parturition for the naloxone- and saline-treated groups, although the time-courses were markedly altered from those observed in rats not subjected to an unfamiliar environment. We conclude that opioid modulation of oxytocin release may play a role in 'spacing' the delivery of successive births during normal parturition.

Naloxone excites oxytocin neurones in the supraoptic nucleus of lactating rats after chronic morphine treatment.

“…This appears to be the first description of opiate tolerance and dependence in an identified peptidergic neuronal system. There is some evidence that an endogenous opioid system modulates oxytocin release during parturition in the rat (Leng, Mansfield, Bicknell, Dean, Ingram, Marsh, Yates & Dyer, 1985;Cutting, Fitzsimons, Gosden, Humphreys, Russell, Scott & Stirland, 1986). The question thus arises as to whether tolerance and dependence ever develop to the endogenous opioids, and whether in particular a withdrawal response occurs under physiological circumstances as a mechanism to evoke hypersecretion of oxytocin.…”

Stimulation of release of -endorphin and oxytocin by prostaglandin F2 in cattle at parturition

“…ß-Endorphin can also be synthesized by human placental tissue (Liotta et al, 1982). In contrast, in cattle submitted to a Caesarean section, ß-endorphin concentrations in blood taken from a branch of the uterine vein were not higher than in samples taken simultaneously from the jugular vein (Dobrinski et al, 1992) (Leng et al, 1985). However, the direct opioid effect on oxytocin neurosecretory terminals is mediated primarily via K-receptors, for which the endogenous ligands are dynorphins and not ß-endorphin (Pesce et al, 1987;Bicknell and Zhao, 1989), but opioids also suppress the release of noradrenaline from neurohypophyseal noradrenergic terminals by acting on an as yet unidentified opioid receptor.…”

“…These mechanisms are par¬ ticularly activated when the animal is disturbed during delivery. In addition to central nervous mechanisms, peripheral opioids, by acting on the posterior pituitary, could have an effect on oxytocin secretion (Leng et al, 1985;.…”

Chronic intracerebroventricular morphine and lactation in rats: dependence and tolerance in relation to oxytocin neurones.

“…This applies to oxytocin secreted in response to a wide range of stimuli (Clarke, Wood, Merrick & Lincoln, 1979;Summy-Long, Miller, Rosella-Dampman, Hartman & Emmert, 1984;Samson, McDonald & Lumpkin, 1985;Cutting, Fitzsimons, Gosden, Humphreys, Russell, Scott & Stirland, 1986), and to endogenously released opioids as well as exogenous opioid, including morphine (Haldar, Hoffman & Zimmerman, 1982;Clarke & Wright, 1984;Keil, Rosella-Dampman, Emmert, Chee & Summy-Long, 1984;Russell & Spears, 1984; Leng, Mansfield, Bicknell, Dean, Ingram, Marsh, Yates & Dyer, 1985). All three families of endogenous opioid peptides are closely associated with both the perikarya and neurosecretory terminals of magnocellular oxytocin neurones although the relative importance of each opioid subtype is unclear (Bicknell, Chapman & Leng, 1985 a;Lincoln & Russell, 1986).…”