Oxytocin and Vasopressin, and the GABA Developmental Shift During Labor and Birth: Friends or Foes?

Abstract

Oxytocin (OT) and vasopressin (AVP) are usually associated with sociability and reduced stress for the former and antidiuretic agent associated with severe stress and pathological conditions for the latter. Both OT and AVP play major roles during labor and birth. Recent contradictory studies suggest that they might exert different roles on the GABA excitatory/inhibitory developmental shift. We reported (Tyzio et al., 2006) that at birth, OT exerts a neuro-protective action mediated by an abrupt reduction of intracellular chloride levels ([Cl−]i) that are high in utero, reinforcing GABAergic inhibition and modulating the generation of the first synchronized patterns of cortical networks. This reduction of [Cl−]i levels is abolished in rodent models of Fragile X Syndrome and Autism Spectrum Disorders, and its restoration attenuates the severity of the pathological sequels, stressing the importance of the shift at birth (Tyzio et al., 2014). In contrast, Kaila and co-workers (Spoljaric et al., 2017) reported excitatory GABA actions before and after birth that are modulated by AVP but not by OT, challenging both the developmental shift and the roles of OT. Here, I analyze the differences between these studies and suggest that the ratio AVP/OT like that of excitatory/inhibitory GABA depend on stress and pathological conditions.

Age and Sex Influences Gamma-aminobutyric Acid Concentrations in the Developing Brain of Very Premature Infants

“…GABA and glutamate play a multitude of metabolic, paracrine and regulatory roles in addition to neurotransmission which are vital during fetal and postnatal brain development [43][44][45][46] . In fact, GABA is considered to exert an excitatory signal in the fetal brain which transitions to the mature inhibitory signal following a developmentally regulated chloride channel switch during perinatal period 7,47 . It remains unclear whether preterm birth alters this signal transition and disrupts further development of the brain and in particular the frontal lobe, which is a prominent region for GABA and glutamatergic system development during late gestation and plays an important role in cognitive outcomes in preterm infants 48 www.nature.com/scientificreports www.nature.com/scientificreports/ which are more common in surviving premature infants 3 .…”

Is Oxytocin “Nature’s Medicine”?

“…Beyond the scope of this review but important to understanding oxytocin and vasopressin is the fact that many other molecules, including dopamine ( Wang and Aragona, 2004 ; Gobrogge and Wang, 2016 ), serotonin ( Dolen, 2015 ), GABA ( Ben-Ari, 2018 ), and opioids ( Meguro et al, 2018 ), interact with these peptides to influence behavior and other functions. Use of drugs, such as opiates, stimulants, and selective serotonin reuptake inhibitors, and diet, can affect both endogenous oxytocin and its receptors with effects that are largely unknown.…”

Pain, Parental Involvement, and Oxytocin in the Neonatal Intensive Care Unit

“…The neonate’s brain is particularly vulnerable to excitotoxic damage, necessitating a balance between excitatory and inhibitory neurotransmission. OXT is responsible for the “developmental switch” in GABA polarity, in that it provides critical neuroprotective and analgesic effects that counteract postnatal excitotoxic damage (Ben-Ari, 2018). More specifically, GABA A receptors are ligand-gated Cl - channels, and the postsynaptic GABAergic signal regulates intracellular Cl - concentration.…”