Estrogen and oxytocin receptors interplay in the medial amygdala to rapidly facilitate social recognition.

The estrogen, 17β-estradiol (E2), rapidly facilitates social recognition in various regions of the social brain network. The medial amygdala (MeA) is heavily involved in the processing of social cues and expresses the three main estrogen receptors (ER): ERα, ERβ, and G Protein-Coupled ER (GPER). All ERs, as well as oxytocin and its receptor (OTR) in the MeA are crucial for social recognition in female mice, suggesting an interplay between ERs and OTR in the rapid facilitation of this social behavior. Here, we demonstrate an interplay between E2 and the three ERs (ERα, ERβ, GPER) with OTR in the MeA underlying the rapid facilitation of social recognition. Ovariectomized female mice were bilaterally infused with a sub-effective dose of OTR antagonist (i.e. the highest dose that does not prevent social recognition) into the MeA via indwelling cannulae, prior to an infusion of either E2 or one of the three ER agonists: ERα agonist PPT, ERβ agonist DPN, GPER agonist G1. A social recognition paradigm designed to measure rapid effects of treatment was employed. In all conditions, the sub-effective dose of OTR antagonist prevented the rapid facilitation of social recognition by E2 and each of the three ER agonists. The results show that E2 and the three main ERs require OTRs to rapidly facilitate social recognition in the MeA of female mice, thus demonstrating a rapid, likely non-genomic, interplay between the estrogen and oxytocin systems in social cognitive processing within a key region of the social brain.