title: Involvement of nitric oxide-cGMP pathway in the antidepressant-like effect of ascorbic acid in the tail suspension test.
abstract: Clinical and preclinical data reported that ascorbic acid has antidepressant properties. The present study was designed to investigate the participation of l-arginine-NO-cGMP pathway in the antidepressant-like effect of ascorbic acid in the tail suspension test (TST) in mice. The antidepressant-like effect of ascorbic acid (1mg/kg, p.o.) in the TST was prevented by the pre-treatment of mice with NMDA (0.1pmol/site, i.c.v.), l-arginine (750mg/kg, i.p., a substrate for nitric oxide synthase) or sildenafil (5mg/kg, i.p., a phosphodiesterase 5 inhibitor). The administration of MK-801 (0.001mg/kg, i.p), 7-nitroindazole (25mg/kg, i.p., a neuronal nitric oxide synthase inhibitor) or ODQ (30pmol/site i.c.v., a soluble guanylate cyclase inhibitor) in combination with a sub-effective dose of ascorbic acid (0.1mg/kg, p.o.) reduced the immobility time in the TST test when compared with either drug alone. None of the results in the TST appears to be due to a nonspecific locomotor effect. Our findings provide evidence that the effect of ascorbic acid in the TST involve an interaction with NMDA receptors and l-arginine-NO-cGMP pathway, contributing to the understanding of the mechanisms underlying the antidepressant-like effect of this vitamin.
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, 88040-900, SC, Brazil.
authors.forename: Morgana
authors.initials: M
authors.lastname: Moretti
authors.forename: Andiara Espindola de
authors.initials: AE
authors.lastname: Freitas
authors.forename: Josiane
authors.initials: J
authors.lastname: Budni
authors.forename: Sinara Castellen Pereira
authors.initials: SC
authors.lastname: Fernandes
authors.forename: Grasiela de Oliveira
authors.initials: Gde O
authors.lastname: Balen
authors.forename: Ana Lúcia Severo
authors.initials: AL
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001120:Arginine / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D006152:Cyclic GMP / Q000378:metabolism*; D003863:Depression / Q000175:diagnosis / Q000188:drug therapy*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D019417:Hindlimb Suspension / Q000379:methods* / Q000502:physiology; D007191:Indazoles / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology
chemical_list: C494582:1H-(1,2,3)oxadiazolo(4,4-a)quinoxalin-1-one; D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D007191:Indazoles; D010069:Oxadiazoles; D010879:Piperazines; D011687:Purines; D011810:Quinoxalines; D013450:Sulfones; D009569:Nitric Oxide; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D001120:Arginine; D000068677:Sildenafil Citrate; D006152:Cyclic GMP; D001205:Ascorbic Acid; C080122:7-nitroindazole