Oxytocin Modulation of Maternal Behavior and Its Association With Immunological Activity in Rats With Cesarean Delivery

Abstract

Oxytocin (OT), a neuropeptide produced in the supraoptic (SON) and paraventricular (PVN) nuclei, is not only essential for lactation and maternal behavior but also for normal immunological activity. However, mechanisms underlying OT regulation of maternal behavior and its association with immunity around parturition, particularly under mental and physical stress, remain unclear. Here, we observed effects of OT on maternal behavior in association with immunological activity in rats after cesarean delivery (CD), a model of reproductive stress. CD significantly reduced maternal interests to the pups throughout postpartum day 1-8. On postpartum day 5, CD decreased plasma OT levels and thymic index but increased vasopressin, interleukin (IL)-1β, IL-6 and IL-10 levels. CD had no significant effect on plasma adrenocorticotropic hormone and corticosterone levels. In the hypothalamus, CD decreased corticotropin-releasing hormone contents in the PVN but increased OT contents in the PVN and SON and OT release from hypothalamic implants. CD also increased c-Fos expression, particularly in the cytoplasm of OT neurons. Lastly, CD depolarized resting membrane potential and increased spike width while increasing the variability of the firing rate of OT neurons in brain slices. Thus, CD can increase hypothalamic OT contents and release but reduce pituitary release of OT into the blood, which is associated with depressive-like maternal behavior, increased inflammatory cytokine release and decreased relative weight of the thymus.

Neural Functions of Hypothalamic Oxytocin and its Regulation

“…This is because pathological blunting of the OTR promoters in 5-HT2A-R and especially in 5-HT2C-R heteroreceptor complexes promotes the development of depression and other types of psychiatric diseases involving disturbances in social behaviors in major depression ( Borroto-Escuela et al, 2021 ). Recent studies in rats further highlight that social stress-evoked increase in hypothalamic OT secretion can account for maternal depression ( Li et al, 2020 ; Li et al, 2021f ). Notably, IAO can benefit new mothers who report moderate sub-clinical levels of depression ( Lindley Baron-Cohen et al, 2021 ).…”

Oxytocin in Women’s Health and Disease

“…As reported in rats, lack of suckling stimulation and bolus OT release during lactation can decrease maternal blood OT levels and cause milk insufficiency and maternal depression in lactating mothers deprived of offspring ( 13 , 95 ) or following cesarean delivery ( 14 ). However, disrupted maternal behavior and lactation performance can be largely improved by IAO during offspring deprivation ( 13 ) or following cesarean delivery ( 14 ). Obviously, disorder in OT system activity contributes to disorders in mental activity while IAO has the potential to correct abnormal social behaviors such as those in schizophrenia and postpartum depression.…”

“…Postpartum depression is associated with disorders on maternal OT system. As reported in rats, lack of suckling stimulation and bolus OT release during lactation can decrease maternal blood OT levels and cause milk insufficiency and maternal depression in lactating mothers deprived of offspring (13,95) or following cesarean delivery (14). However, disrupted maternal behavior and lactation performance can be largely improved by IAO during offspring deprivation (13) or following cesarean delivery (14).…”

“…The somatodendritic OT release can be in synchrony with the firing activity under physiological conditions, such as suckling stimulation ( 12 ). It can be independent of the firing activity under some pathological conditions, such as maternal depression following offspring deprivation ( 13 ) and cesarean delivery ( 14 ).…”

“…Notably, women with peripartum exposure to synthetic OT have a higher relative risk of depressive or anxiety disorder diagnosis or antidepressant/anxiolytic prescription within the first year postpartum than women without synthetic OT exposure ( 89 ). This is likely due to the suppression of excessive OT on OT neuronal activity via a mechanism of post-excitation inhibition of OT neuronal activity ( 14 , 23 , 90 ).…”