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 matinginduced
facilitation of social fear extinction.