The Oxytocin Receptor: From Intracellular Signaling to Behavior

Abstract

The many facets of the oxytocin (OXT) system of the brain and periphery elicited nearly 25,000 publications since 1930 (see FIGURE 1 , as listed in PubMed), which revealed central roles for OXT and its receptor (OXTR) in reproduction, and social and emotional behaviors in animal and human studies focusing on mental and physical health and disease. In this review, we discuss the mechanisms of OXT expression and release, expression and binding of the OXTR in brain and periphery, OXTR-coupled signaling cascades, and their involvement in behavioral outcomes to assemble a comprehensive picture of the central and peripheral OXT system. Traditionally known for its role in milk let-down and uterine contraction during labor, OXT also has implications in physiological, and also behavioral, aspects of reproduction, such as sexual and maternal behaviors and pair bonding, but also anxiety, trust, sociability, food intake, or even drug abuse. The many facets of OXT are, on a molecular basis, brought about by a single receptor. The OXTR, a 7-transmembrane G protein-coupled receptor capable of binding to either Gα or Gα proteins, activates a set of signaling cascades, such as the MAPK, PKC, PLC, or CaMK pathways, which converge on transcription factors like CREB or MEF-2. The cellular response to OXT includes regulation of neurite outgrowth, cellular viability, and increased survival. OXTergic projections in the brain represent anxiety and stress-regulating circuits connecting the paraventricular nucleus of the hypothalamus, amygdala, bed nucleus of the stria terminalis, or the medial prefrontal cortex. Which OXT-induced patterns finally alter the behavior of an animal or a human being is still poorly understood, and studying those OXTR-coupled signaling cascades is one initial step toward a better understanding of the molecular background of those behavioral effects.

Tracking oxytocin functions in the rodent brain during the last 30 years: From push‐pull perfusion to chemogenetic silencing

“…1,2 Here, in accordance with the focus of this special issue of the Journal of Neuroendocrinology celebrating its first volume in 1989, we give a very personal view and track our own lines of research, starting with the description of OXT release within limbic brain regions using the method of push-pull perfusion during suckling in the freely moving lactating rat, as published in this very first volume. The interest in the OXT system has especially been developed in the last 30 years by the discovery of a plethora of behavioural and physiological effects, both in animals and humans.…”

“…1 Furthermore, it provided the final proof that central OXT does not originate from peripheral sources. 1 Furthermore, it provided the final proof that central OXT does not originate from peripheral sources.…”

“…1 In this context, anatomical discoveries by S. Ramon y Cajal should be mentioned, who were the first to describe a neuronal pathway from the SON to the posterior pituitary in 1894. 1 In this context, anatomical discoveries by S. Ramon y Cajal should be mentioned, who were the first to describe a neuronal pathway from the SON to the posterior pituitary in 1894.…”

Neurobiological Aspects of Face Recognition: The Role of Oxytocin

“…Central release of OT is a major regulator of numerous social behavioral processes, including social communication, social recognition, social memory, interpersonal cooperation, and decision-making (Jurek and Neumann, 2018). …”

“…Particularly, rs2254298 contributes to amygdala volume and the response to salient social cues in face recognition tests (Marusak et al, 2015). Other SNPs in the OXTR dictate the peculiarities of pro-social cooperative behaviors and the functional activity of the amygdala during the emotional face-matching task (Haas et al, 2013; Jurek and Neumann, 2018). …”