151. Involvement of nitric oxide-cGMP pathway in the antidepressant-like effect of ascorbic acid in the tail suspension test.
- Author
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Moretti M, Freitas AE, Budni J, Fernandes SC, Balen Gde O, and Rodrigues AL
- Subjects
- Animals, Arginine pharmacology, Ascorbic Acid pharmacology, Depression diagnosis, Disease Models, Animal, Dizocilpine Maleate pharmacology, Enzyme Inhibitors pharmacology, Exploratory Behavior drug effects, Female, Hindlimb Suspension physiology, Indazoles pharmacology, Mice, N-Methylaspartate pharmacology, Oxadiazoles pharmacology, Piperazines pharmacology, Purines pharmacology, Quinoxalines pharmacology, Signal Transduction drug effects, Sildenafil Citrate, Sulfones pharmacology, Antidepressive Agents therapeutic use, Ascorbic Acid therapeutic use, Cyclic GMP metabolism, Depression drug therapy, Hindlimb Suspension methods, Nitric Oxide metabolism, Signal Transduction physiology
- 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., (Copyright © 2011. Published by Elsevier B.V.)
- Published
- 2011
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