BEHAVIORAL ABNORMALITIES IN MALE-MICE LACKING NEURONAL NITRIC-OXIDE SYNTHASE

Is addition to its role in blood vessel(1,2) and macrophage(3,4) function, nitric oxide (NO) is a neurotransmitter(5) found in high densities in emotion-regulating brain regions(6-8). Mice with targeted disruption of neuronal NO synthase (nNOS) display grossly normal appearance, locomotor activity, breeding(9), long-term potentiation and long-term depression(11). The nNOS(-) mice are resistant to neural stroke damage following middle cerebral artery ligation(12). Although CO2-induced cerebral vasodilatation in wild-type mice is NO-dependent, in nNOS(-) mice this vasodilation is unaffected by NOS inhibitors(13). Establishing a behavioural role for NO has, until now, not been feasible, as NOS inhibitor drugs can only be administered acutely and because their pronounced effects on blood pressure and other body functions obfuscate behavioural interpretations. We now report a large increase in aggressive behaviour and excess, inappropriate sexual behaviour in nNOS(-) mice.