An oxytocin receptor antagonist infused into the supraoptic nucleus attenuates intranuclear and peripheral release of oxytocin during suckling in conscious rats.

We tested the hypothesis that oxytocin (OXT) released within the supraoptic nucleus (SON) during suckling in lactating rats facilitates its own intranuclear release and thereby stimulates its secretion into blood during the milk ejection reflex. In the first study, to examine the positive feedback action of OXT released within the SON, microdialysates of the SON area were sampled before and during suckling. Either vehicle (1.0 microliter) or an OXT receptor antagonist (50 ng/microliters) was infused adjacent to the microdialysis probe into the SON area before suckling began. Compared to the corresponding presuckling values (100%), the OXT content in microdialysates sampled during the suckling period increased after vehicle treatment (to 501 +/- 174%; P < 0.01), whereas infusion of the OXT antagonist significantly (P < 0.05) attenuated the rise in the release of OXT during suckling (130 +/- 22.0%). In the second study, the influence of intranuclear OXT on release of OXT into the blood during suckling was examined. Compared to those in rats infused with vehicle into both SON before suckling started (100%), injection of the OXT antagonist decreased the concentration of OXT in plasma (to 32.1 +/- 5.50%; P < 0.05) and the milk transfer to the pups during the suckling period (to 30.2 +/- 13.3%; P < 0.01). Although the neuroendocrine response to suckling was attenuated in rats receiving the OXT antagonist, maternal behavior, assessed as the time at which six to eight pups began suckling and the time from the onset until the occurrence of the third milk ejection reflex, was unaffected. These findings provide evidence for a receptor-mediated positive feedback action of OXT on its own release within the SON during suckling. The amplification of intranuclear release of OXT is needed for the release of appropriate amounts of OXT into the bloodstream to stimulate milk transfer to the suckling pups.