From Parental Behavior to Sexual Function: Recent Advances in Oxytocin Research

Current Sexual Health Reports https://doi.org/10.1007/s11930-024-00386-1 From Parental Behavior to Sexual Function: Recent Advances in Oxytocin Research Joseph Dale II2,4 · Mitchell T. Harberson1,2 · Jennifer W. Hill1,2,3 Accepted: 2 May 2024 © The Author(s) 2024 Abstract Purpose of Review Oxytocin plays many diverse roles in physiological and behavioral processes, including social activity, parental nurturing, stress responses, and sexual function. In this narrative review, we provide an update on the most noteworthy recent findings in this fascinating field. Recent Findings The development of techniques such as serial two-photon tomography and fiber photometry have provided a window into oxytocin neuroanatomy and real-time neuronal activity during social interactions. fMRI and complementary mapping techniques offer new insights into oxytocin's influence on brain activity and connectivity. Indeed, oxytocin has recently been found to influence the acquisition of maternal care behaviors and to mediate the influence of social touch on brain development and social interaction. Additionally, oxytocin plays a crucial role in male sexual function, affecting erectile activity and ejaculation, while its role in females remains controversial. Recent studies also highlight oxytocin's interaction with other neuropeptides, such as melanin-concentrating hormone, serotonin, and arginine vasopressin, influencing social and affective behaviors. Finally, an update is provided on the status of clinical trials involving oxytocin as a therapeutic intervention. Summary The exploration of oxytocin's complexities and its interplay with other neuropeptides holds promise for targeted treatment in various health and disease contexts. Overall, these findings contribute to the discovery of new and specific pathways to allow therapeutic targeting of oxytocin to treat disorders. Keywords Oxytocin · Paraventricular Hypothalamic Nucleus · Social Behavior · Sexual Behavior · Maternal Behavior · Neuroanatomy Introduction Oxytocin is a well-known and highly-studied nonapeptide hormone produced by neurons in the supraoptic nucleus (SON) and the paraventricular nucleus of the hypothalamus Joseph Dale II and Mitchell T. Harberson are joint first authors. * Jennifer W. Hill 1 Center for Diabetes and Endocrine Research, University of Toledo College of Medicine, Toledo, OH, USA 2 Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH, USA 3 Department of Obstetrics and Gynecology, University of Toledo College of Medicine, Toledo, OH, USA 4 Department of Biology, University of Toledo College of Medicine, Toledo, OH, USA (PVH). Magnocellular oxytocin neurons in these areas project to the posterior pituitary gland where they release oxytocin into circulation [1]. The most well-known function of oxytocin is inducing contractions in the uterus during labor and in the breast tissue during breast feeding. Oxytocin can also be released centrally in the brain to modulate the activity of neurons and neural circuits to regulate a range of social and non-social processes. Oxytocin research has primarily focused on its regulation of social behaviors such as parental nurturing, pair bonding, partner preference, sensory processing, empathy, and sexual function [2, 3]. How oxytocin modifies such a large range of social behaviors is a major open question. One of the dominant hypotheses, the “social salience” hypothesis, claims that oxytocin does not promote prosocial behaviors but rather increases the salience of social stimuli by acting on the mesolimbic dopamine system[4]. The primary evidence for this hypothesis is that oxytocin action is context-specific rather than unidirectional in Vol.:(0123456789) Current Sexual Health Reports its actions. For example, oxytocin increases love, trust, and empathy only toward in-group members while promoting aggression toward out-group members[5, 6]. Inconsistencies in the literature are also explained by oxytocin action being sex-specific[7, 8], species-specific[9, 10], and specific to the stage of development[11]. Despite this complexity, scientists have used advances in genetic, molecular, and anatomical biology to help understand the underlying mechanisms controlling behaviors. As detailed below, these studies represent a major advance in our understanding of oxytocin. New Neuroanatomical Insights New advances in genetic models, technology, and computer software [12] have enhanced our understanding of oxytocinergic neuroanatomy, activity, and interactivity with other neuronal cell types. Recently, Son and colleagues have used whole-brain mapping techniques to visualize oxytocin's distribution, projections, and overlap with oxytocin receptor (OXTR) expression in mice [13••]. The largest clusters of oxytocin neurons were found in the PVH, SON, accessory nuclei (AN), and the often-overlooked tuberal nucleus (TU), which had nearly as many neurons as the PVH. Imaging the separate projections of these four nuclei yielded data that is well-supported by other recent publications [14, 15]. The PVH projected widely to nine functional circuits; the AN and SON may regulate these circuits through their projections to the PVH. The TU had no long-range projections. Interestingly, most projection areas had reciprocal connections with oxytocinergic circuits. Although most oxytocin neurons project to midbrain and hindbrain regions, OXTR is expressed primarily in cortical regions. Indeed, when the oxytocin projectome data were compared to whole-brain OXTR expression, no correlation was found except in the thalamus and medulla. Furthermore, this publication found oxytocin fibers contacting the surface of the lateral, third, and fourth ventricles [13••]. Taken together, these results support the well-documented hypothesis that oxytocin action is partially mediated through transmission into the cerebrospinal fluid (CSF) [16]. More specifically, oxytocin secretion into the CSF of the lateral ventricle has been found to be important for its actions in the cerebral cortex[17]. This mechanism may explain how oxytocin interacts with the high cortical expression of OXTR found by Son and colleagues. However, other studies have found most regions that express OXTR have at least a small number of oxytocinergic projections[9]; therefore, oxytocin action is likely mediated through both CSF and direct transmission. The non-ventricular oxytocin projections that seemingly have no local OXTR expression could be instances of oxytocin acting on other receptors such as vasopressin receptors[18] or TRPV1 receptors[19]. An interesting alternative hypothesis was proposed by Grinevich and coworkers that states these oxytocinergic projections may be secreting glutamate from these synapses while secreting oxytocin non-synaptically (i.e. somatodendritically)[20]. Indeed, evidence suggests the fear-related behavioral effects of oxytocin neurons are mediated through synapt (...truncated)