Behavioural abnormalities in male mice lacking neuronal nitric oxide synthase

In addition to its role in blood vessel^1,2and macrophage^3,4function, nitric oxide (NO) is a neurotransmitter⁵found in high densities in emotion-regulating brain regions^6–8. Mke with targeted disruption of neuronal NO synthase (nNOS) display grossly normal appearance, locomotor activity, breeding⁹, long-term potentiation¹⁰and long-term depression¹¹. The nNOS⁻mice are resistant to neural stroke damage following middle cerebral artery ligation¹². Although CO₂-induced cerebral vasodilatation in wild-type mice is NO⁻dependent, in nNOS" mice this vasodilation is unaffected by NOS inhibitors¹³. 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.