Oxytocin (OT) knock-out mice fail to recognize familiar conspecifics after
repeated social exposures, despite normal olfactory and spatial learning ab
ilities. OT treatment fully restores social recognition. Here we demonstrat
e that OT acts in the medial amygdala during the initial exposure to facili
tate social recognition. OT given before, but not after, the initial encoun
ter restores social recognition in OT knock-out mice. Using c-Fos immunorea
ctivity (Fos-IR) as a marker of neuronal activation in this initial encount
er, we found similar neuronal activation in the wild-type (WT) and OT knock
-out mouse in olfactory bulbs, piriform cortex, cortical amygdala, and the
lateral septum. Wild-type, but not OT knock-out mice exhibited an induction
of Fos-IR in the medial amygdala. Projections sites of the medial amygdala
also failed to show a Fos-IR induction in the OT knock-out mice. OT knock-
out, but not WT, mice showed dramatic increases in Fos-IR in the somatosens
ory cortex and the hippocampus, suggesting alternative processing of social
cues in these animals. With site-specific injections of OT and an OT antag
onist, we demonstrate that OT receptor activation in the medial amygdala is
both necessary and sufficient for social recognition in the mouse.