The Neuropeptide Oxytocin Facilitates Pro-Social Behavior and Prevents Social Avoidance in Rats and Mice

Abstract

Social avoidance and social phobia are core symptoms of various psychopathologies but their underlying etiology remains poorly understood. Therefore, this study aims to reveal pro-social effects of the neuropeptide oxytocin (OT), under both basal and stressinduced social avoidance conditions in rodents using a social preference paradigm. We initially show that intracerebroventricular (i.c.v.) application of an OT receptor antagonist (OTR-A) in naïve male rats (0.75 mg/5 ml), or mice (20 mg/2 ml), reduced social exploration of a novel con-specific indicative of attenuated social preference. Previous exposure of male rats to a single social defeat resulted in loss of their social preference and social avoidance, which could be restored by i.c.v. infusion of synthetic OT (0.1 mg/5 ml) 20 min before the social preference test. Although the amygdala has been implicated in both social and OT-mediated actions, bilateral OTR-A (0.1 mg/1 ml) or OT (0.01 mg/1 ml) administration into various subnuclei of the amygdala did not affect basal or stress-induced social preference behavior, respectively. Finally, we demonstrate the social specificity of these OT-mediated effects by showing that neither an arginine vasopressin V1a receptor antagonist (0.75 mg/5 ml, i.c.v.) nor the anxiogenic drug pentylenetetrazol (15 mg/kg, i.p.) altered social preference, with OTR-A not affecting non-social anxiety on the elevated plus-maze. Overall, the data indicate that the basal activity of the endogenous brain OT system is sufficient to promote natural occurring social preference in rodents while synthetic OT shows potential to reverse stress-induced social avoidance and might thus be of use for treating social phobia and social dysfunction in humans.

Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms

“…Oxytocin (OXT) and argininevasopressin (AVP), closely-related nonapeptides, are mainly synthesized in the supraoptic and paraventricular nuclei of the hypothalamus. OXT plays key regulatory roles in affiliative and social behaviors as has been revealed by substantial studies in rodents [1][2][3] and other species [4,5], including humans [6]. Similarly, AVP is also involved in the regulation of social behaviors including social preference [7], social memory [8], social bonding [9], and aggression [10].…”

Animal personality and state–behaviour feedbacks: a review and guide for empiricists

“…For example, high testosterone can increase aggressiveness, but aggressive behaviour can also drive up testosterone levels, giving rise to a positive feedback. Positive feedbacks also exist between social behaviours and oxytocin [34][35][36], and between behaviour, life histories, and corticosterone responses [37,38]. Of course, neuroendocrine systems themselves are characterized by feedbacks [39,40] and these feedbacks can potentially stabilize personalities even if behaviour does not strongly affect hormones [37].…”

Can Understanding Social Preferences in Rodents Lead to Novel Pharmacotherapies for Social Anxiety and Avoidance in Psychiatric Disorders?

“…The studies performed by Lukas et al (2011) suggest that brain areas other than the amygdala, are involved, and the effect is not likely to be explained by the anxiolytic effects of oxytocin.…”

“…Now the oxytocin system is an exciting potential pharmacological target with a tremendous body of basic science supporting its role in regulating social cognition. Although the early years of oxytocin research were driven by a basic science curiosity of how the brain controls behavior, increasingly, studies like those presented by Lukas et al (2011) are motivated by translational implications. Indeed, our knowledge of the biology of the social brain, as determined by animal studies, will likely be the foundation of novel pharmacotherapies to treat a host of disorders with deficits in the social domain.…”

“…In addition, social phobias and social anxiety can have devastating impacts on the development of healthy social relationships. A study published in this issue by Lukas et al (2011) from Inga Neumann's group in Regensburg, Germany, used rats and mice to explore the role of the neuropeptide, oxytocin, on the preference for social stimuli and a form of social anxiety induced by social defeat. These preclinical studies in animals have important implications for developing novel pharmacotherapies for psychiatric disorders with muted social interest and elevated social withdrawal.…”