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Oxytocin (OT), a hypothalamic neuropeptide, applied through nasal approach (IAO), could improve maternal health during lactation that is disrupted by mother–baby separation; however, the regulation of IAO effects on maternal behaviors and lactation as well as the underlying mechanisms remain unclear. Using lactating rats, we observed effects of intermittent pup deprivation (PD) with and without IAO on maternal behaviors and lactation as well as the activity of OT neurons in the supraoptic nucleus (SON) and the activity of hypothalamic pituitary-adrenal axis, key factors determining the milk-letdown reflex during lactation and maternal behaviors. The results showed that PD reduced maternal behaviors and lactation efficiency of rat dams as indicated by significantly longer latency to retrieve their pups and low litter’s body weight gains during the observation, respectively. In addition, PD caused early involution of the mammary glands. IAO partially improved these changes in rat dams, which was not as significant as IAO effects on control dams. In the SON, PD decreased c-Fos and increased glial fibrillary acidic protein (GFAP) filaments significantly; IAO made PD-evoked c-Fos reduction insignificant while reduced GFAP filament significantly in PD dams. IAO tended to increase the levels of phosphorylated extracellular signal-regulated kinases (pERK) 1/2 in PD dams. Moreover, PD+IAO significantly increased plasma levels of dam adrenocorticotropic hormone and corticosterone but not OT levels. Lastly, PD+IAO tended to increase the level of corticotropin-releasing hormone in the SON. These results indicate that PD disrupts maternal behaviors and lactation by suppressing the activity of hypothalamic OT-secreting system through expansion of astrocytic processes, which are partially reversed by IAO through removing astrocytic inhibition of OT neuronal activity. However, the improving effect of IAO on the maternal health could be compromised by simultaneous activation of hypothalamic pituitary-adrenocortical axis.

Effects of Intranasal Oxytocin on Pup Deprivation-Evoked Aberrant Maternal Behavior and Hypogalactia in Rat Dams and the Underlying Mechanisms