Mating-induced release of oxytocin in the mouse lateral septum: Implications for social fear extinction

In mammals, some physiological conditions are associated with the high brain oxytocin (OXT) system activity. These include lactation in females and mating in males and females, both of which have been linked to reduced stress responsiveness and anxiolysis. Also, in a murine model of social fear conditioning (SFC), enhanced brain OXT signaling in lactating mice, specifically in the lateral septum (LS), was reported to underlie reduced social fear expression. Here, we studied the effects of mating in male mice on anxiety-related behaviour, social (and cued) fear expression and its extinction, and the activity of OXT neurons reflected by cFos expression and OXT release in the LS and amygdala. We further focused on the involvement of brain OXT in the mating-induced facilitation of social fear extinction. We could confirm the anxiolytic effect of mating in male mice irrespective of the occurrence of ejaculation. Further, we found that only successful mating resulting in ejaculation (Ej+) facilitated social fear extinction, whereas mating without ejaculation (Ej-) did not. In contrast, mating did not affect cues fear expression. Using the cellular activity markers cFos and pErk, we further identified the ventral LS (vLS) as a potential region participating in the effect of ejaculation on social fear extinction. In support, microdialysis experiments revealed a rise in OXT release within the LS, but not the amygdala, during mating. Finally, infusion of an OXT receptor antagonist into the LS before mating or into the lateral ventricle (icv) after mating demonstrated a significant role of brain OXT receptor-mediated signaling in the mating-induced facilitation of social fear extinction. •Successful mating with ejaculation facilitates social fear extinction.•Septal activity correlates with ejaculation-induced social fear extinction facilitation.•Mating induces oxytocin (OXT) release within the lateral septum (LS).•LS-OXT receptor inhibition abolishes mating-induced facilitation of social fear extinction.