Abstract

Oxytocin has been suggested as a promising new treatment for neurodevelopmental disorders. However, important gaps remain in our understanding of its mode of action, in particular, to what extent oxytocin modulates social and non-social behaviours and whether its effects are generalizable across both sexes. Here we investigated the effects of a range of oxytocin doses on social and non-social behaviours in C57BL/6N mice of both sexes. As the striatum modulates social and non-social behaviours, and is implicated in neurodevelopmental disorders, we also conducted a pilot exploration of changes in striatal protein expression elicited by oxytocin. Oxytocin increased prepulse inhibition of startle but attenuated the recognition memory in male C57BL/6N mice. It increased social interaction time and suppressed the amphetamine locomotor response in both sexes. The striatum proteome following oxytocin exposure could be clearly discriminated from saline controls. With the caveat that these results are preliminary, oxytocin appeared to alter individual protein expression in directions similar to conventional anti-psychotics. The proteins affected by oxytocin could be broadly categorized as those that modulate glutamatergic, GABAergic or dopaminergic signalling and those that mediate cytoskeleton dynamics. Our results here encourage further research into the clinical application of this peptide hormone, which may potentially extend treatment options across a spectrum of neurodevelopmental conditions.

Highlights

  • Oxytocin has a recognised role in lactation and parturition

  • We hypothesized that peripherally injected oxytocin would improve performance in social and non-social tasks and alter protein expression in a similar direction to that reported for anti-psychotic medication

  • Previous oxytocin exposure had no impact on the baseline startle response (p = 0.214), data from mice exposed to a single or repeated dose was combined for further analysis in each sex separately

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Summary

Introduction

Oxytocin has a recognised role in lactation and parturition. It has central binding sites in the limbic system and basal ganglia [1] and is appreciated to be involved in the regulation of a wide variety of social and non-social behaviours [2]. Oxytocin has been proposed to have utility in neurodevelopmental disorders of social processing and PLOS ONE | DOI:10.1371/journal.pone.0145638. Oxytocin Effects on Behaviour and Protein Expression in C57BL/6N Mice Oxytocin has been proposed to have utility in neurodevelopmental disorders of social processing and PLOS ONE | DOI:10.1371/journal.pone.0145638 December 30, 2015

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