INTRODUCTION: Social memory—the ability to recognize and remember conspecifics—is essential for adaptive social behaviors. Previous studies using genetic and pharmacological approaches have demonstrated that both the inactivation of the prodynorphin gene (Pdyn⁻/⁻) and the blockade of κ-opioid receptors (KOR) enhance partner recognition in mice, while KOR activation impairs social memory. These findings suggest that reduced KOR signaling and the resulting neuronal disinhibition facilitate social memory processing. However, the specific neuronal populations expressing KOR that are involved in this process remain unclear.

AIM(S): The aim of this study was to determine whether selective deletion of KORs from oxytocinergic or serotonergic neurons affects social memory performance, and whether this is accompanied by changes in monoamine levels in the prefrontal cortex and striatum—key areas for reward and social behavior.

METHOD(S): We assessed social memory in genetically modified mice with selective deactivation of KOR on oxytocin (Oprk1OxtCre) or serotonin (Orpk1TphCreERT2) expressing neurons. Mice were exposed once to an unfamiliar, same-sex juvenile animal, and social memory was assessed by decreased interaction time with the same partner during a second encounter. Using high-performance liquid chromatography (HPLC), we also evaluated changes in monoamine concentrations within the prefrontal cortex and striatum.

RESULTS: Preliminary findings indicate that female Oprk1OxtCre mice exhibit prolonged social memory retention, resembling the phenotype observed in Pdyn⁻/⁻ mice. In contrast, Oprk1Tph2CreERT2 mice displayed normal sociability and intact social memory.

CONCLUSIONS: Taken together, our results indicate a sex-dependent link between oxytocin and dynorphin signaling in social memory regulation, and suggest that KOR signaling on oxytocinergic neurons, rather than serotonergic neurons, is crucial in this process.

FINANCIAL SUPPORT: National Science Centre, Poland OPUS 2019/35/B/NZ7/03477