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In a specific mouse model of social fear conditioning (SFC), both OXT and NPS reverse social fear and reinstate social preference behaviour. In case of OXT, this effect has been linked to the lateral septum3. We could also show that activation of the endogenous OXT system as seen in lactation is accompanied by lack of SFC-induced social fear. Thus, enhanced OXT signaling specifically in the lateral septum seems responsible for enhanced resilience of lactating mice against trauma.
As OXT and NPS share many behavioural effects, we tested possible interactions between these neuropeptide systems. Thus, NPS activated hypothalamic OXT neurons, which express the NPS receptors. Both NPS and OXT exert an anxiolytic effect directly within the PVN, but in case of NPS, this essentially requires local OXT activity: When local OXT actions were prevented (either pharmacologically or chemogenetically) the anxiolytic effect of NPS was prevented. 4
Thus, the multiple neuropeptide effects described within the brain in particular modulating socio-emotional behaviours likely rely on their context-specific interactions. Supported by DFG, BMBF and EU.