Brain oxytocin: how puzzle stones from animal studies translate into psychiatry

Abstract

The neuropeptide oxytocin has attracted great attention of the general public, basic neuroscience researchers, psychologists, and psychiatrists due to its profound pro-social, anxiolytic, and "anti-stress" behavioral and physiological effects, and its potential application for treatment of mental diseases associated with altered socio-emotional competence. During the last decade, substantial progress has been achieved in understanding the complex neurobiology of the oxytocin system, including oxytocinergic pathways, local release patterns, and oxytocin receptor distribution in the brain, as well as intraneuronal oxytocin receptor signaling. However, the picture of oxytocin actions remains far from being complete, and the central question remains: "How does a single neuropeptide exert such pleotropic actions?" Although this phenomenon, typical for many of about 100 identified neuropeptides, may emerge from the anatomical divergence of oxytocin neurons, their multiple central projections, distinct oxytocin-sensitive cell types in different brain regions, and multiple intraneuronal signaling pathways determining the specific cellular response, further basic studies are required. In conjunction, numerous reports on positive effects of intranasal application of oxytocin on human brain networks controlling socio-emotional behavior in health and disease require harmonic tandems of basic researchers and clinicians. During the COVID-19 crisis in 2020, oxytocin research seems central as question of social isolation-induced inactivation of the oxytocin system, and buffering effects of either activation of the endogenous system or intranasal application of synthetic oxytocin need to be thoroughly investigated.

Cardiovascular protective properties of oxytocin against COVID-19

“…Social stress is important etiology of CV malfunctions because it can disrupt normal behavior, neuroendocrine, and autonomic responses. By facilitating positive social interactions, suppressing sympathetic outflow and reducing fear and anxiety, OXT can counteract the deleterious effects of social stress and its associated unhealthy life-style, hypertension, and coronary artery diseases [ 48 , 49 ].…”

“…OXT can reduce stress-elicited neuroendocrine, autonomic, and behavioral responses [ 53 ], which can be used to prevent the brain-heart syndrome [ 129 ]. In addition, OXT also has anti-depressive effects [ 130 ] and may be used to relieve social isolation-associated depression in COVID-19 patients [ 48 ]. Thus, OXT/OTR signaling contributes to cardio-protection through diverse approaches in COVID-19.…”

Links Between the Neurobiology of Oxytocin and Human Musicality

“…The foregoing section has, of necessity, over-simplified the physiological effects of oxytocin on neural tissue in animals, and more in-depth reviews are available (e.g., Bakos et al, 2018 ; Jurek and Neumann, 2018 ; Mitre et al, 2018 ; Neumann and Landgraf, 2019 ). However, some discussion of animal-based research is warranted because, given that the peptide is highly conserved in evolution it is likely that similar wide-ranging molecular and cellular mechanisms are operative in the human brain (see also Grinevich and Neumann, 2020 ). From a behavioral perspective, animal studies reveal that oxytocin has an important role in pair-bonding and maternal attachment, in moderating affiliative behaviors and conspecific social recognition, and in modulating the formation and maintenance of episodic memories, whether they be positive or negative.…”

“…During revision of this manuscript, a review was published that emphasized the importance of studying the biology of oxytocin systems in animals to better understand the translational potential of this peptide in psychiatry and mental health (Grinevich and Neumann, 2020 ). The reader is encouraged to access this review to complement the more focussed emphasis on human musicality described herein.…”

Oxytocin Receptor Signaling in Vascular Function and Stroke

“…Since its original cloning and characterization by Kimura et al (1992), to more recent predictions of its three dimensional structure (Busnelli et al, 2016), the human oxytocin receptor (OXTR) has garnered special attention for its role as a potential therapeutic target in a wide array of physiological and behavioral disorders. Several recent reviews have comprehensively covered the impact of OXTR signaling upon peripheral and central control of behavior and physiological functions including osmoregulatory, stress modulation, and memory (Jurek and Neumann, 2018;Grinevich and Neumann, 2020). By contrast, this review will survey the role of OXTR-mediated cellular and molecular pathways regulating vascular function, with a special focus on mechanisms of cerebrovascular disease and the receptor's putative disease-modifying role in the post-stroke environment, which may be amenable to therapeutic targeting.…”