• Cristiano R Jesse, Ethel A Wilhelm, Cristiani F Bortolatto, João B T Rocha, and Cristina W Nogueira.
• Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
• Eur. J. Pharmacol. 2010 Jun 10;635(1-3):135-41.

AbstractThe 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 0.5-5mg/kg, decreased the immobility time in the forced swimming and tail suspension tests. Pretreatment with l-arginine (750mg/kg, intraperitoneal, i.p., a nitric oxide precursor), sildenafil (5mg/kg, i.p., a phosphodiesterase 5 inhibitor) or S-nitroso-N-acetyl-penicillamine (25microg/site, intracerebroventricular, i.c.v., a nitric oxide donor) reversed the reduction in the immobility time elicited by bis selenide (1mg/kg, p.o.) in the tail suspension test. Bis selenide (0.1mg/kg, p.o., a subeffective dose) produced a synergistic antidepressant-like effect with N(G)-nitro-L-arginine (0.3mg/kg, i.p., an inhibitor of nitric oxide synthase) or 7-nitroindazole (25mg/kg, i.p., a specific neuronal nitric oxide synthase inhibitor) in the tail suspension test. Pretreatment of animals with methylene blue (10mg/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 (30pmol, 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 (1mg/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.

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