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 nitric oxide synthase gene (nNOS-/-) exhibit significantly impaired maternal aggression, but increased male aggression, suggesting that nitric oxide (NO) produced by nNOS has opposite actions in maternal and male aggression. In contrast, mice lacking the endothelial nitric oxide synthase gene (eNOS-/-) exhibit almost no male aggression, suggesting that NO produced by eNOS facilitates male aggression. In the present study, maternal aggression in eNOS-/- mice was examined and found to be normal relative to wild-type (WT) mice in terms of the percentage displaying aggression, the average number of attacks against a male intruder, and the total amount of time spent attacking the male intruder. The eNOS-/- females also displayed normal pup retrieval behavior. Because a significant elevation of citrulline, an indirect marker of NO synthesis, occurs in neurons of the hypothalamus of lactating WT mice in association with maternal aggression, we examined the brains of eNOS-/- females for citrulline immunoreactivity following an aggressive encounter. The aggressive eNOS-/- females exhibited a significant elevation of citrulline in the medial preoptic nucleus and the subparaventricular zone of the hypothalamus relative to unstimulated lactating eNOS-/- females. Taken together, these results suggest that NO produced by eNOS neither facilitates nor inhibits maternal aggression and that NO produced by eNOS has a different role in maternal and male aggression.