Oxytocin Receptors Regulate Social Preference in Zebrafish

Jenny Landin,Lars Westberg,David Lagman,Dan Larhammar,Petronella Kettunen,Daniel Hovey,Anna Zettergren,Bo Xu

doi:10.1038/s41598-020-61073-4

Jenny Landin, Lars Westberg + Show 6 more

Open Access

https://doi.org/10.1038/s41598-020-61073-4

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Abstract

With a strong tendency to socialise, the zebrafish is a useful model to study social behaviour, with implications for better treatments of social impairments, for instance in autism spectrum disorders. Although oxytocin is crucial for social behaviour in mammals, the importance of the fish orthologue – isotocin or zebrafish oxytocin (zOT) – for social behaviour in zebrafish is unclear. The aims of this study were firstly, to elucidate the receptor specificity of zOT and the related vasotocin or zebrafish vasopressin (zVP; the orthologue of mammalian vasopressin) and the nonpeptidergic oxytocin receptor antagonist L-368,899, and secondly to investigate if L-368,899 inhibits social preference in zebrafish. The potencies of ligands were evaluated for zOT/zVP family receptors in HEK293 cells. Adult and larval zebrafish were treated with L-368,899 or vehicle and subsequently assessed for social behaviour and anxiety (adults only). The antagonist L-368,899 specifically inhibited the two zOT receptors, but not the two zVP-1 receptors. The antagonist decreased social preference in adult and larval zebrafish. It did not affect anxiety in adults. These results indicate that endogenous zOT, and possibly zVP, is involved in social behaviour in zebrafish via either or both of the two zOT receptors, and show promise for future explorations of the anatomy and evolution of networks underlying social behaviour.

Highlights

In our in vitro studies, the two zebrafish oxytocin (zOT) receptor subtypes and two zebrafish vasopressin (zVP) receptor-1 subtypes were individually expressed in HEK293 cells (Fig. 1)
Recent studies suggest that exogenous OT ligands modulates social behaviour in adult zebrafish[42], the relevance of endogenous zOT and its two receptor subtypes – Oxtr and Oxtrl – for social behaviour in adult and larval zebrafish remains to be clarified
Our initial pharmacological in vitro studies were primarily aimed to explore the effects of zOT and the OT receptor antagonist L-368,899 on the two zOT receptors as well as the two most closely related zVP receptors, encoded by the genes avpr1aa and avpr1ab

Summary

Introduction

Specific ablation of zOT neurons in the posterior tuberculum at the embryonic stage resulted in reduced shoaling behaviour and reduced social preference in adult zebrafish[43]. To increase our understanding of the relation between social behaviour and the zOT receptors in adult and larval zebrafish, we used L-368,899 to block the zOT receptors, and measure the effect on social preference, shoaling behaviour, and anxiety-like behaviour. Our behavioural studies using L-368,899 imply that endogenous zOT, and possibly zVP, regulates the types of social preference studied here through actions on either or both of the zOT receptors in both adult and larval zebrafish, but not (or less so) via the two VP-1 receptors.

Results

Conclusion