Differential effects of nitric oxide synthase inhibitors on anxiety in unstressed and stressed mice

Effects of selective nitric oxide synthase (NOS) inhibitors, 7-nitroindazole (7-NI), a selective inhibitor of neuronal nitric oxide synthase (nNOS) and aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase (iNOS) on anxiety in unstressed and stressed mice were investigated using elevated plus maze (EPM) test and light-dark test (LDT). 7-NI (20 and 40 mg/kg, ip) produced anti-anxiety effect in unstressed mice but not in stressed mice. AG (50 and 100 mg/kg, ip) produced anxiolytic effect in stressed mice and failed to produce the similar effect in unstressed mice. Nitrite levels were increased in stressed mice, but not in unstressed mice, exposed to EPM and LDT for 5 min. Increased nitrite levels in stressed mice were attenuated by AG, but not by 7-NI. The effects of AG were enhanced by pyrrolidine-dithio-carbamate (PDTC), an inhibitor of NF-kappaB induction, in stressed mice. The results suggest the possible role of inducible nitric oxide synthase in stress-induced anxiogenesis as compared to unstressed mice, where neuronal form of NOS may plays predominant role.