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) (5-100 mg/kg; oral route, p.o.). The antiimmobility effect of (PhSe)(2) (5 mg/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) (0.1 mg/kg, p.o.) produced a synergistic antidepressant-like effect with N(G)-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; 30 pmol/site i.c.v., a specific inhibitor of soluble guanylate cyclase (sGC)], fluoxetine and imipramine in the TST. (PhSe)(2) (50-100 mg/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.
Savegnago
Lucielli
L
Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Jesse
Cristiano Ricardo
CR
Pinto
Larissa Garcia
LG
Rocha
Joao Batista Teixeira
JB
Barancelli
Daniela Aline
DA
Nogueira
Cristina Wayne
CW
Zeni
Gilson
G
D000818:Animals; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D001120:Arginine / Q000502:physiology*; D001555:Benzene Derivatives / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006162:Guanylate Cyclase / Q000502:physiology*; D019417:Hindlimb Suspension / Q000523:psychology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013550:Swimming / Q000523:psychology
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D001555:Benzene Derivatives; D016566:Organoselenium Compounds; C061132:diphenyldiselenide; D009569:Nitric Oxide; D001120:Arginine; D006162:Guanylate Cyclase