A novel antianxiety- like activity of amino guanidine in stressed mice: evidence of regulation by no: CGMP modulation

An investigation on possible regulation of antianxiety- like activity of amino guanidine in stressed mice by nitric oxide: cyclic guanosine monophosphate (NO: cGMP) modulation was made. Stressed mice were administered with amino guanidine and tested on elevated plus maze and light/dark box. NO: cGMP modulators (L-arginine, Methylene blue, Bay-607550, 8-Br-cGMP) were administered as pre-treatments in the separate groups of amino guanidine- treated stressed mice and modulation of the noted effect of amino guanidine in stressed mice was observed. Diazepam (2 mg/kg, i.p.) was employed as comparator drug. Amino guanidine (50 mg/kg, i.p.) produced a significant antianxiety- like activity in stressed mice (p<0.05). The noted antianxiety- like activity of amino guanidine in stressed mice was accompanied by a significant decrease in plasma nitrite levels (p<0.05). L-Arginine (100 mg/kg, i.p.), a nitric oxide (NO) donor, significantly attenuated the noted antianxiety- like activity of amino guanidine in stressed mice (p<0.05). This attenuation of antianxiety- like activity of amino guanidine in stressed mice was accompanied by a significant increase in plasma nitrite levels in stressed mice (p<0.05). Methylene blue (1mg/kg, i.p.), a soluble gunylate cyclase (sGC) inhibitor, served to significantly enhance the noted antianxiety- like activity of amino guanidine in stressed mice (p<0.05). Pre-treatment with a cGMP facilitator (Bay-607550; 3 mg/kg, i.p.) and a cGMP analogue (8-Br-cGMP; 1mM, i.p.) failed to bring any significant change in the noted antianxiety- like activity of amino guanidine in stressed mice. It is noteworthy that no significant increase (p<0.05) was observed in plasma cGMP levels in stressed mice, treated with combination of amino guanidine and Bay-607550. The results of the present study strengthen the possibility of a novel antianxiety- like activity of amino guanidine in stressed mice and serve to provide an evidence of possible regulation of the antianxiety- like activity of amino guanidine in stressed mice by NO: cGMP modulation.