The Role of the Oxytocin/Arginine Vasopressin System in Animal Models of Autism Spectrum Disorder

Abstract

The nonapeptides oxytocin (OXT) and arginine vasopressin (AVP) are two key mediators in regulating various aspects of mammalian social behaviours. There are several lines of evidence that genetic variants of the OXT/AVP system exist in autism spectrum disorder (ASD) and that this system is dysfunctional at least in some ASD entities. These findings have stimulated the interest to perform studies testing the potential therapeutic application of OXT/AVP in ASD. In this respect animal models are critical for investigating the pathophysiology and for compound screening leading to new therapeutic approaches. Based on findings in animal models that show alterations of the OXT/AVP system, it has been hypothesised that single- or multiple-dose administration or the stimulation of endogenous release can improve several social deficits. Here we comprehensively review the role of the OXT/AVP system in social recognition, social interaction and maternal behaviour in the light of different ASD animal models and patient studies. We further discuss implications for OXT/AVP-related pharmacological interventions to alleviate social deficits in ASD in the future.

Neonatal Oxytocin Treatment Ameliorates Autistic-Like Behaviors and Oxytocin Deficiency in Valproic Acid-Induced Rat Model of Autism

“…Oxytocin in the brain is synthesized and secreted by the paraventricular nucleus (PVN) and supraoptic nucleus (SON) ( Stoop, 2012 ), and OXT-containing neural projections and OXT receptors (Oxtr) are widely distributed in the brain areas involved in regulating social behavior ( Caldwell, 2017 ; Song and Albers, 2017 ). Oxt ( Ferguson et al, 2000 ; Ferguson et al, 2001 ) or Oxtr ( Sala et al, 2011 ; Pobbe et al, 2012a , b ) knockout (KO) mice have been reported to exhibit less social communication and interaction, along with impaired social cognitive memory and other altered behaviors relevant to ASD ( Zhang et al, 2017 ). Central infusion or peripheral injection of OXT has been shown to promote social approach ( Lukas et al, 2011 ; Teng et al, 2016 ), pair bonding ( Bales and Carter, 2003 ; Bales et al, 2007 ; Ross et al, 2009 ), and social memory ( Popik and van Ree, 1991 ; Benelli et al, 1995 ) in rodents.…”

“…Although the underlying mechanisms of ASD are still largely unknown, deficiency in the OXT systems has been suggested to be involved in its development ( Preti et al, 2014 ; Zhang et al, 2017 ) because of the critical role of OXT in regulating social behaviors. Deficits in OXT-immunoreactive (OXT-ir) neurons and peptide levels were observed in several monogenic mouse models of autism, including BTBR mice ( Silverman et al, 2010b ), CNTNAP2 ( Penagarikano et al, 2015 ) KO mice and MAGEL2 ( Meziane et al, 2015 ) KO mice.…”

Sex Differences in Salivary Oxytocin and Cortisol Concentration Changes during Cooking in a Small Group

“…The nonapeptide oxytocin (OT) promotes social affiliation and bond formation, and functions to reduce anxiety and dampen the stress response in mammalian species [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. OT also plays a role in mediating the stress-buffering and anxiolytic effects of close social interactions [ 16 , 17 ]. Impairments in the OT system are found in patients with autism spectrum disorder (ASD), borderline personality disorder, and anxiety disorders [ 3 , 18 , 19 , 20 , 21 , 22 , 23 ].…”

Salivary Oxytocin Concentration Changes during a Group Drumming Intervention for Maltreated School Children

“…Recent studies have suggested that oxytocin (OT) plays a role in social memory and behavior [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. OT has positive effects on social and emotional processes in healthy subjects and some individuals diagnosed with a variety of psychiatric disorders [ 29 , 30 , 31 , 32 , 33 ]. Nasal application of OT in subjects with ASD with or without comorbid intellectual disability has been shown to improve social interactions [ 34 , 35 , 36 , 37 , 38 ].…”