Effects of estrogen on social recognition and oxytocin regulating synaptic plasticity

Estrogens play an important role in the regulation of female social recognition; however, their mechanisms have not yet been elucidated. The present study established a mouse model of adolescent ovariectomy (Ovx) supplemented with a physiological dose of estradiol benzoate (EB, 10 µg/kg). Familiar-novel individual identification, urine odor discrimination, and social memory behaviors were assessed after adulthood. The results showed that Ovx-induced impairment of individual identification, urine odor discrimination, and social memory 24 h after testing were significantly improved by EB supplementation. Meanwhile, EB restored 17β-estradiol (17β-E₂) and oxytocin (OT) levels in the brain and serum of Ovx females. EB upregulated the expression level of OT receptor (OTR) protein and increased the numbers of ERα-ir and ERβ-ir cell in the medial amygdala (MeA). Electrophysiological studies further showed that OT (10 and 100 nM) promoted the induction and maintenance of long-term potentiation (LTP) in CA2 region of the hippocampal slices in vitro, which could be abolished by pretreatment with OTR antagonist l-368,899. 17β-E₂ (10 nM) not only promoted LTP, but also synergistically enhanced the promotion effect of 10 nM OT on LTP, which was eliminated by pretreatment with ERs antagonists ICI182780. These results suggest that estrogen promotes the OT system in the MeA and synergistically promotes OT increasing the synaptic plasticity of the hippocampus through ERs, which enhances social odor discrimination and social memory, and ultimately improves social recognition in female mice.