Involvement of NO-cGMP pathway in anti-anxiety effect of aminoguanidine in stressed mice

In the present study, effect of aminoguanidine (12.5, 25 and 50 mg/kg, i.p.), a selective inhibitor of inducible nitric oxide synthase, was evaluated for its anti-anxiety activity in stressed mice employing elevated plus maze, open field test, light/dark test and social interaction test. Restraint stress induced by immobilizing for 6 h enhanced an anxiety-like behavior and increased plasma nitrite levels in mice. Only the highest dose (50 mg/kg) employed of aminoguanidine attenuated the stress-induced anxiety-like behavior and decreased plasma nitrite levels. There was no significant anxiolytic effect of aminoguanidine in unstressed mice. Sildenafil (1 mg/kg i.p.), was used to explore the probable mechanism of anti-anxiety activity of aminoguanidine through NO-cGMP signaling. Aminoguanidine (50 mg/kg) attenuated the anxiogenic effect of sildenafil. Aminoguanidine and sildenafil per se and in combination did not affect the locomotor activity of stressed and unstressed mice as compared to their respective control groups. Thus, aminoguanidine produced anti-anxiety activity in stressed mice through iNOS-NO-cGMP pathway. (C) 2009 Elsevier Inc. All rights reserved.