The Oxytocin Receptor: From Intracellular Signaling to Behavior

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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 _ior Gα _qproteins, 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.

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SNAREs--engines for membrane fusion.

Reinhard Jahn, Richard H. Scheller (2006)

Since the discovery of SNARE proteins in the late 1980s, SNAREs have been recognized as key components of protein complexes that drive membrane fusion. Despite considerable sequence divergence among SNARE proteins, their mechanism seems to be conserved and is adaptable for fusion reactions as diverse as those involved in cell growth, membrane repair, cytokinesis and synaptic transmission. A fascinating picture of these robust nanomachines is emerging.

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Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States.

Ronald C Kessler, Maria Petukhova, Nancy Sampson … (2012)

Estimates of 12-month and lifetime prevalence and of lifetime morbid risk (LMR) of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) anxiety and mood disorders are presented based on US epidemiological surveys among people aged 13+. The presentation is designed for use in the upcoming DSM-5 manual to provide more coherent estimates than would otherwise be available. Prevalence estimates are presented for the age groups proposed by DSM-5 workgroups as the most useful to consider for policy planning purposes. The LMR/12-month prevalence estimates ranked by frequency are as follows: major depressive episode: 29.9%/8.6%; specific phobia: 18.4/12.1%; social phobia: 13.0/7.4%; post-traumatic stress disorder: 10.1/3.7%; generalized anxiety disorder: 9.0/2.0%; separation anxiety disorder: 8.7/1.2%; panic disorder: 6.8%/2.4%; bipolar disorder: 4.1/1.8%; agoraphobia: 3.7/1.7%; obsessive-compulsive disorder: 2.7/1.2. Four broad patterns of results are most noteworthy: first, that the most common (lifetime prevalence/morbid risk) lifetime anxiety-mood disorders in the United States are major depression (16.6/29.9%), specific phobia (15.6/18.4%), and social phobia (10.7/13.0%) and the least common are agoraphobia (2.5/3.7%) and obsessive-compulsive disorder (2.3/2.7%); second, that the anxiety-mood disorders with the earlier median ages-of-onset are phobias and separation anxiety disorder (ages 15-17) and those with the latest are panic disorder, major depression, and generalized anxiety disorder (ages 23-30); third, that LMR is considerably higher than lifetime prevalence for most anxiety-mood disorders, although the magnitude of this difference is much higher for disorders with later than earlier ages-of-onset; and fourth, that the ratio of 12-month to lifetime prevalence, roughly characterizing persistence, varies meaningfully in ways consistent with independent evidence about differential persistence of these disorders. Copyright © 2012 John Wiley & Sons, Ltd.

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Oxytocin, vasopressin, and the neurogenetics of sociality.

Z Donaldson, L Young (2008)

There is growing evidence that the neuropeptides oxytocin and vasopressin modulate complex social behavior and social cognition. These ancient neuropeptides display a marked conservation in gene structure and expression, yet diversity in the genetic regulation of their receptors seems to underlie natural variation in social behavior, both between and within species. Human studies are beginning to explore the roles of these neuropeptides in social cognition and behavior and suggest that variation in the genes encoding their receptors may contribute to variation in human social behavior by altering brain function. Understanding the neurobiology and neurogenetics of social cognition and behavior has important implications, both clinically and for society.

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Author and article information

Journal

Title: Physiological Reviews

Abbreviated Title: Physiological Reviews

Publisher: American Physiological Society

ISSN (Print): 0031-9333

ISSN (Electronic): 1522-1210

Publication date Created: July 01 2018

Publication date (Print): July 01 2018

Volume: 98

Issue: 3

Pages: 1805-1908

Affiliations

[1 ]Department of Behavioural and Molecular Neurobiology, Institute of Zoology, University of Regensburg, Regensburg, Germany

Article

DOI: 10.1152/physrev.00031.2017

PubMed ID: 29897293

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Self URI (article page): https://www.physiology.org/doi/10.1152/physrev.00031.2017

The Oxytocin Receptor: From Intracellular Signaling to Behavior

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Abstract

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Most cited references 1,105

SNAREs--engines for membrane fusion.

Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States.

Oxytocin, vasopressin, and the neurogenetics of sociality.

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Journal

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Article

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