Maternal aggression in endothelial nitric oxide synthase-deficient mice

Lactating female rodents protect their pups by expressing fierce aggression , termed maternal aggression, toward intruders. Mice lacking the neuronal n itric oxide synthase gene (nNOS-/-) exhibit significantly impaired maternal aggression, but increased male aggression, suggesting that nitric oxide (N O) produced by nNOS has opposite actions in maternal and male aggression. I n contrast, mice lacking the endothelial nitric oxide synthase gene (eNOS-/ -) exhibit almost no male aggression, suggesting that NO produced by eNOS f acilitates male aggression. In the present study, maternal aggression in eN OS-/- mice was examined and found to be normal relative to wild-type (WT) m ice in terms of the percentage displaying aggression, the average number of attacks against a male intruder, and the total amount of time spent attack ing the male intruder. The eNOS-/-females also displayed normal pup retriev al behavior. Because a significant elevation of citrulline, an indirect mar ker of NO synthesis, occurs in neurons of the hypothalamus of lactating WT mice in association with maternal aggression, we examined the brains of eNO S-/females for citrulline immunoreactivity following an aggressive encounte r. The aggressive eNOS-/- females exhibited a significant elevation of citr ulline in the medial preoptic nucleus and the subparaventricular zone of th e hypothalamus relative to unstimulated lactating eNOS-/- females. Taken to gether, these results suggest that NO produced by eNOS neither facilitates nor inhibits maternal aggression and that NO produced by eNOS has a differe nt role in maternal and male aggression. (C) 2000 Academic press.