title: Antidepressant-like effect of quercetin in bulbectomized mice and involvement of the antioxidant defenses, and the glutamatergic and oxidonitrergic pathways.
abstract: Olfactory bulbectomy (OB) is an animal model of depression that can mimic symptoms that are characteristic of depressive patients, such as behavioral, neurochemical and neuromorphological changes. Quercetin decreased the immobility time in the forced swimming test and tail suspension test. With the open field test, quercetin did not alter the locomotor activity of mice and in the splash test, quercetin increased the time spent grooming. The repeated treatment with quercetin (25mg/kg, for 14days) reversed the behavioral hyperactivity induced by OB in the open field test and was able to prevent depressant-like effects in the forced swimming test and tail suspension test. Regarding oxidative stress, OB reduced the levels of glutathione and increase the activity of superoxide dismutase and lipid hydroperoxide content (LOOH) in the hippocampus. Only the increase in LOOH levels was reversed by treatment with quercetin. In a further series of experiments with non-bulbectomized mice, the antidepressant effect of quercetin in the tail suspension test was reversed by the pretreatment of mice with NMDA, l-arginine or sildenafil. The administration of methylene blue and 7-nitroindazole, in combination with an underactive dose of quercetin (5mg/kg, p.o.), decreased the immobility time in the tail suspension test compared with the use of drug alone. There was no significant change in locomotor activity in the open field test. Our results suggest that the antidepressant effect of quercetin is dependent on the inhibition of the NMDA receptors and/or synthesis of nitric oxide. In addition, considering the reduction of LOOH levels on the hippocampus, we verify that the antioxidant effects of quercetin also contribute to its antidepressive potential. These data contribute to the understanding of the mechanisms involved in the antidepressant effect of quercetin and reinforce the involvement of the NMDA receptors and the nitric oxide on the pathophysiology of depression.
authors.affiliation: Centro de Ciências da Saúde, CCS- Programa de Pós-Graduação em Ciências Farmacêuticas/UNIVALI-Itajaí, SC, Brazil. Electronic address: iandrah@hotmail.com.
authors.forename: Iandra
authors.initials: I
authors.lastname: Holzmann
authors.affiliation: Centro de Ciências da Saúde, CCS- Programa de Pós-Graduação em Ciências Farmacêuticas/UNIVALI-Itajaí, SC, Brazil.
authors.forename: Luísa Mota
authors.initials: LM
authors.lastname: da Silva
authors.affiliation: Centro de Ciências da Saúde, CCS- Programa de Pós-Graduação em Ciências Farmacêuticas/UNIVALI-Itajaí, SC, Brazil.
authors.forename: José Afonso
authors.initials: JA
authors.lastname: Corrêa da Silva
authors.affiliation: Centro de Ciências da Saúde, CCS- Programa de Pós-Graduação em Ciências Farmacêuticas/UNIVALI-Itajaí, SC, Brazil.
authors.forename: Viviane Miranda Bispo
authors.initials: VM
authors.lastname: Steimbach
authors.affiliation: Centro de Ciências da Saúde, CCS- Programa de Pós-Graduação em Ciências Farmacêuticas/UNIVALI-Itajaí, SC, Brazil.
authors.forename: Márcia Maria
authors.initials: MM
authors.lastname: de Souza
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology*; D009830:Olfactory Bulb / Q000601:surgery*; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D000068677:Sildenafil Citrate / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D000975:Antioxidants; D007191:Indazoles; D005473:Fluoxetine; D016202:N-Methylaspartate; D001120:Arginine; D011794:Quercetin; D000068677:Sildenafil Citrate; D008751:Methylene Blue; C080122:7-nitroindazole
keywords: Depression; NMDA; Nitric oxide; Olfactory bulbectomy; Oxidative stress; Quercetin