Seminar by Prof. Dr. Inga D. Neumann

University of Regensburg (Germany)

Brain oxytocin in rodent socio-emotional behavior: from social preference to social fear

The neuropeptide oxytocin currently attracts attention from preclinical and clinical scientists due to its profound anxiolytic, anti-stress and pro-social properties. Specifically, oxytocin promotes not only reproductive behaviours such as mating, bonding and maternal behaviours, but also social preference, empathy and social memory. Up-regulation of the brain oxytocin system found, e.g. during the peripartum period or after mating, was found to result in oxytocin-dependent anxiolysis and attenuated stress and fear response. Its anxiolytic and pro-social actions can also be induced by synthetic OXT in humans via the intranasal route of administration. Although it has been proposed as a potential therapeutic agent for disorders associated with socio-emotional deficits, detailed mechanisms of action are largely unknown.
Here, I will present data on OXT actions on naturally occurring social preference behavior in rats and mice as assessed in the social preference and avoidance test [1]. Further, in a murine model of social fear – the social fear conditioning (SFC) paradigm - we revealed that OXT reversed or prevented social fear [2], an effect which was localized within the dorso-lateral septum. In contrast, OXT impairs cued fear extinction indicating its specific role in a social context. Our results imply that OXT exerts differential effects on social versus cued fear extinction suggesting OXT as an add-on drug in the treatment of social anxiety disorders.
With the aim to reveal the molecular mechanisms underlying its anxiolytic effects within the hypothalamic paraventricular nucleus (PVN) we studied OXT receptor-mediated signaling cascades such as the MAP kinase pathway [3], subsequent regulation of the expression of the anxiogenic neuropeptide CRF [4] and activation of neuronal TRPV channels and, consequently, Ca²⁺ influx [5].
Our result indicate that details regarding gender-, dose- and context-dependent effects at behavioral and neuronal levels are needed, before OXT can be considered a safe treatment option. Supported by DFG, EU, BMBF.

BIBLIOGRAPHY

(1) Lukas M et al. 2011. Neuropsychopharmacology 36:2159-68
(2) Zoicas I, Slattery DA, Neumann ID (2014) Neuropsychopharmacology
(3) Jurek B et al. PLoS One 2012;7(5): e37060
(4) Jurek B et al., J Neurosci 2015; 35:12248-60. doi:10.1523/ JNEUROSCI.1345-14.2015.
(5) van den Burg E et al., Neuropsychopharmacology. 2015, doi: 10.1038/npp.2015.147.