Involvement of l-arginine–nitric oxide–cyclic guanosine monophosphate pathway in the antidepressant-like effect of bis selenide in the mouse tail suspension test

The present study investigated a possible antidepressant-like effect of bis selenide by using the forced swimming and the tail suspension tests. The involvement of the l-arginine–nitric oxide–cyclic guanosine monophosphate signaling pathway in the antidepressant-like action of bis selenide was investigated. Bis selenide, given by oral route at doses of 0.5–5 mg/kg, decreased the immobility time in the forced swimming and tail suspension tests. Pretreatment with l-arginine (750 mg/kg, intraperitoneal, i.p., a nitric oxide precursor), sildenafil (5 mg/kg, i.p., a phosphodiesterase 5 inhibitor) or S-nitroso-N-acetyl-penicillamine (25 μg/site, intracerebroventricular, i.c.v., a nitric oxide donor) reversed the reduction in the immobility time elicited by bis selenide (1 mg/kg, p.o.) in the tail suspension test. Bis selenide (0.1 mg/kg, p.o., a subeffective dose) produced a synergistic antidepressant-like effect with NG-nitro-l-arginine (0.3 mg/kg, i.p., an inhibitor of nitric oxide synthase) or 7-nitroindazole (25 mg/kg, i.p., a specific neuronal nitric oxide synthase inhibitor) in the tail suspension test. Pretreatment of animals with methylene blue (10 mg/kg, i.p., an inhibitor of nitric oxide synthase and soluble guanylate cyclase) or 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (30 pmol, i.c.v., a specific inhibitor of soluble guanylate cyclase), at subeffective doses, caused a synergistic effect with bis selenide in the tail suspension test. Bis selenide (1 mg/kg, p.o.), at an effective dose in the forced swimming and tail suspension tests, caused a significant decrease in the mouse cerebral nitrate/nitrite levels. The antidepressant-like effect of bis selenide in the tail suspension test is dependent on the inhibition of the l-arginine–nitric oxide–cyclic guanosine monophosphate pathway.