Aggressive behavior in male mice lacking the gene for neuronal nitric oxide synthase requires testosterone

Nitric oxide acts as a neural messenger in both the central and peripheral nervous systems. Mice with targeted disruption of the neuronal isoform of nitric oxide synthase (nNOS -/-) are extremely aggressive relative to wild-type (WT) mice. Male nNOS -/- mice exhibit an increase in the number and duration of aggressive encounters compared to WT animals when tested in a variety of paradigms used to test rodent aggression. This inappropriate aggressive behavior has only been observed in male nNOS -/- mice; nNOS -/- females, like female WT mice, exhibit Little or no aggression. The present study sought to test the dependence of increased aggressive behavior in nNOS -/- males on testosterone. Intact nNOS -/- males exhibited elevated levels of aggression relative to intact WT males. Castration reduced aggression in both WT and nNOS -/- males to equivalent low levels. Testosterone replacement restored aggression to precastration levels in both genotypes. These data provide evidence that increased aggressive behavior of nNOS -/- mice, Like aggression in WT mice, is testosterone-dependent. (C) 1997 Elsevier Science B.V.