Antidepressant-like effect of folic acid: Involvement of NMDA receptors and L-arginine-nitric oxide-cyclic guanosine monophosphate pathway.
Antidepressant-like activity of folic acid in forced swimming test and in the tail suspension test was demonstrated previously by our group. In this study we investigated the involvement of N-methyl-d-aspartate (NMDA) receptors and l-arginine-nitric oxide (NO)-cyclic guanosine monophosphate pathway in its antidepressant-like effect in the forced swimming test in mice. The antidepressant-like effect of folic acid (10 nmol/site, i.c.v.) was prevented by the pretreatment of mice with NMDA (0.1 pmol/site, i.c.v.), l-arginine (750 mg/kg, i.p., substrate for nitric oxide synthase), S-nitroso-N-acetyl-penicillamine (SNAP, 25 microg/site, i.c.v, a NO donor) or sildenafil (5 mg/kg, i.p., phosphodiesterase 5 inhibitor). The administration of 7-nitroindazole (25 and 50 mg/kg, i.p., a specific neuronal nitric oxide synthase (nNOS) inhibitor) or methylene blue (20 mg/kg, i.p., direct inhibitor of both nitric oxide synthase and soluble guanylate cyclase) in combination with a sub-effective dose of folic acid (1 nmol/site, i.c.v.) reduced the immobility time in the FST as compared with either drug alone. Together the results suggest that the antidepressant-like effect of folic acid in the forced swimming test is dependent on an inhibition of either NMDA receptors or NO and cGMP synthesis.
Brocardo
Patrícia de Souza
Pde S
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900, Florianópolis-SC, Brazil.
Budni
Josiane
J
Lobato
Kelly Ribas
KR
Kaster
Manuella Pinto
MP
Rodrigues
Ana Lúcia S
AL
D000818:Animals; D000928:Antidepressive Agents; D001120:Arginine / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D005492:Folic Acid / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013550:Swimming / Q000523:psychology; D014803:Vitamin B Complex / Q000494:pharmacology*
D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D007191:Indazoles; D020030:Nitric Oxide Donors; D016194:Receptors, N-Methyl-D-Aspartate; D014803:Vitamin B Complex; D009569:Nitric Oxide; D016202:N-Methylaspartate; D026423:S-Nitroso-N-Acetylpenicillamine; D005492:Folic Acid; D001120:Arginine; D006152:Cyclic GMP; D008751:Methylene Blue; C080122:7-nitroindazole