Oxytocin and Animal Models for Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) is a group of complex neurodevelopmental conditions characterized by deficits in social communication and by repetitive and stereotypic patterns of behaviors, with no pharmacological treatments available to treat these core symptoms. Oxytocin is a neuropeptide that powerfully regulates mammalian social behavior and has been shown to exert pro-social effects when administered intranasally to healthy human subjects. In the last decade, there has been a significant interest in using oxytocin to treat social behavior deficits in ASD. However, little attention has been paid to whether the oxytocin system is perturbed in subgroups of individuals with ASD and whether these individuals are likely to benefit more from an oxytocin treatment. This oversight may in part be due to the enormous heterogeneity of ASD and the lack of methods to carefully probe the OXT system in human subjects. Animal models for ASD are valuable tools to clarify the implication of the oxytocin system in ASD and can help determine whether perturbation in this system should be considered in future clinical studies as stratifying biomarkers to inform targeted treatments in subgroups of individuals with ASD. In this chapter, we review the literature on genetic- and environmental-based animal models for ASD, in which perturbations in the oxytocin system and/or the effect of oxytocin administration on the ASD-associated phenotype have been investigated.

Oxytocin administration in neonates shapes the hippocampal circuitry and restores social behavior in a mouse model of autism

“…Oxytocin (OT) and its signaling pathway, the OT-system, are disrupted in several animal models of neurodevelopmental disorders characterized with autism-like phenotypes (1,2).…”

“…Indeed, knock-out mouse models of Ot (3,4), oxytocin receptor (Oxtr) (5-7), or ADP-ribosyl cyclase (Cd38) (8,9) genes show changes in social behavior. In addition, several rodent models of autism spectrum disorders (ASD) endophenotypes due either to the inactivation of genes such as Fmr1, Cntnap2, Magel2, Oprm1, or to environmental valproic acid exposure (VPA), exhibit a disruption of the brain OT-system (1). Many of these models have in common at least two constant phenotypes (10).…”

Oxytocin as a Modulator of Synaptic Plasticity: Implications for Neurodevelopmental Disorders

“…The last two decades have been enriched with studies exploring the behavioral effects of the pro-social oxytocin (OXT) neuropeptide (Heinrichs et al, 2003 , 2009 ; Kirsch et al, 2005 ; Guastella et al, 2008a , b ; Marsh et al, 2010 ; Guastella and MacLeod, 2012 ) and its mechanisms of action (Blume et al, 2008 ; Jurek et al, 2012 ; van den Burg et al, 2015 ). In parallel, several clinical and preclinical studies have focused on the therapeutic potential of OXT, mainly to treat social behavior deficits (Guastella and Hickie, 2016 ; Wagner and Harony-Nicolas, 2017 ). However, little attention has been paid to the possible implication of the OXT system in neurodevelopmental disorders and to whether perturbation in OXT may contribute to the social behavior phenotype.…”

Laboratory Findings in Twins Suffering from Autism—Case Report

“…Previous results suggest that OXT and arginine vasopressin (AVP) may play a role in the etiopathogenesis of ASD [20]. The effects of oxytocin on social cognition and behavior have recently attracted considerable attention and numerous papers have researched the possible role of oxytocin as therapeutic agent to treat ASD [21,22]. Animal models also demonstrated that the neuropeptide oxytocin plays an important role in social recognition and bonding.…”