Diphenyl diselenide exerts antidepressant-like and anxiolytic-like effects in mice: Involvement of l-arginine-nitric oxide-soluble guanylate cyclase pathway in its antidepressant-like action

This study investigated the possible antidepressant-like and anxiolytic-like effects of diphenyl diselenide, (PhSe)2 in mice. The involvement of l-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway in the antidepressant-like effect was also evaluated. The immobility times in the tail suspension test (TST) and forced swimming test (FST) were reduced by (PhSe)2 (5–100mg/kg; oral route, p.o.). The antiimmobility effect of (PhSe)2 (5mg/kg, p.o.) in the TST was prevented by pretreatment of mice with l-arginine [a substrate for nitric oxide synthase (NOS)], methylene blue [an inhibitor of NO synthase and sGC] and sildenafil [a phosphodiesterase 5 inhibitor]. Furthermore, a sub-effective dose of (PhSe)2 (0.1mg/kg, p.o.) produced a synergistic antidepressant-like effect with NG-nitro-l-arginine [l-NNA; 0.3mg/kg, i.p. inhibitor of NOS], (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one [ODQ; 30pmol/site i.c.v., a specific inhibitor of soluble guanylate cyclase (sGC)], fluoxetine and imipramine in the TST. (PhSe)2 (50–100mg/kg, p.o.) induced anxiolytic-like effect in the elevated plus-maze test and light/dark box. Together the results indicate that (PhSe)2 elicited significant antidepressant-like and anxiolytic-like effects. The antidepressant-like action caused by (PhSe)2 seems to involve an interaction with l-arginine-NO-cGMP pathway.