Prosocial effects of oxytocin in two mouse models of autism spectrum disorders

Abstract

Clinical evidence suggests that oxytocin treatment improves social deficits and repetitive behavior in autism spectrum disorders (ASDs). However, the neuropeptide has a short plasma half-life and poor ability to penetrate the blood-brain barrier. In order to facilitate the development of more bioavailable oxytocinergic compounds as therapeutics to treat core ASD symptoms, small animal models must be validated for preclinical screens. This study examined the preclinical utility of two inbred mouse strains, BALB/cByJ and C58/J, that exhibit phenotypes relevant to core ASD symptoms. Mice from both strains were intraperitoneally administered oxytocin, using either acute or sub-chronic regimens. Acute oxytocin did not increase sociability in BALB/cByJ; however, sub-chronic oxytocin had significant prosocial effects in both BALB/cByJ and C58/J. Increased sociability was observed 24 hours following the final oxytocin dose in BALB/cByJ, while prosocial effects of oxytocin emerged 1–2 weeks post-treatment in C58/J. Furthermore, acute oxytocin decreased motor stereotypy in C58/J and did not induce hypoactivity or anxiolytic-like effects in an open field test. This study demonstrates that oxytocin administration can attenuate social deficits and repetitive behavior in mouse models of ASD, dependent on dose regimen and genotype. These findings provide validation of the BALB/cByJ and C58/J models as useful platforms for screening novel drugs for intervention in ASDs and for elucidating the mechanisms contributing to the prosocial effects of oxytocin.

Translational and therapeutic potential of oxytocin as an anti-obesity strategy: Insights from rodents, nonhuman primates and humans

“…Future investigations should examine if intermittent or pulsatile delivery [83,[196][197][198][199][200][201] of OT will extend its effectiveness and circumvent reductions in OTR binding known to occur in the CNS following chronic CNS infusions [170,171]. In addition, studies should examine if inhibition of oxytocinase activity [64], PEGylation [202][203][204] or conjugation to albumin [205] in combination with oral delivery [206] will produce prolonged effects and eliminate the need for multiple injections.…”

Autism genes are selectively targeted by environmental pollutants including pesticides, heavy metals, bisphenol A, phthalates and many others in food, cosmetics or household products

“…Oxytocin plays a generally beneficial role in sociability in animal models [129,130]. Autism related behaviour is observed in oxytocin or oxytocin receptor knockout mice [131].…”

Melanin concentrating hormone modulates oxytocin-mediated marble burying

“…OT has been implicated as a potential therapeutic for autism (Ho and Blevins, 2013; Lukas and Neumann, 2013; Salmina et al, 2013), since intranasal OT administrations in ASD patients increases social communication and improves the timing of social responses (Watanabe et al, 2014). Acute administration of OT has been shown to decrease repetitive stereotypical behaviors in inbred mouse models of ASD (Teng et al, 2013). In Asperger’s Syndrome clinical trials, OT treatment, improved social cooperation and social aptitude (Andari et al, 2010) and reduced repetitive behaviors (Hollander et al, 2003).…”