Inhibition of the medial amygdala disrupts escalated aggression in lactating female mice after repeated exposure to male intruders

Abstract Virgin female laboratory mice readily express maternal care when co-housed with dams and pups. However, pup-sensitized virgins fail to express maternal aggression on a single session of testing. To study whether repeated testing would affect the onset and dynamics of maternal aggression we tested dams and their accompanying virgins from postpartum day 4 to 6. Repeated testing led to escalated aggression towards male intruders in dams, but virgins never developed aggression. In dams, inhibition of the medial amygdala using DREADD (designer receptors exclusively activated by designer drugs) vectors carrying the hM4Di receptor blocked the expected increase in maternal aggression on the second testing day. Our data support that the onset of maternal aggression is linked to physiological changes occurring during motherhood, and that medial amygdala, a key centre integrating vomeronasal, olfactory and hormonal information, enables the expression of escalated aggression induced by repeated testing.