Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas. Programa de Pós-Graduação em Neurociências. / Made available in DSpace on 2012-10-24T14:28:39Z (GMT). No. of bitstreams: 1
262305.pdf: 1360095 bytes, checksum: cebb4ec2f79926d9bedfaac6f68ad9cb (MD5) / Major depression is a chronic, severe, life threatening disease, and one of the most prevalent forms of mental illness in the occidental world. The monoamine theory of depression postulates that this disease results from a deficiency of brain monoaminergic activity, however other neural systems and biochemical process, like oxidative stress, appear to be involved in its pathogenesis. á-Tocopherol, the most active and abundant form of vitamin E, is the major fat-soluble chain-breaking antioxidant of the human organism. Studies have shown that major depression is accompanied by a significant reduction in serum vitamin E concentrations, but no study was conducted in animal models of depression. This study investigated the effect of acute and chronic treatment with á-tocopherol in the forced swim test (FST) and in the tail suspension test (TST), two widely used behavioral tests that predict the efficacy of antidepressant treatments. The oral treatment with á-tocopherol at the doses of 30 and 100 mg/kg reduced the immobility time in the FST and in the TST. The i.c.v. administration of á-tocopheryl phosphate was also able to reduce the immobility time in the FST (0.1 and 1 nmol/site) and in the TST (0.01 nmol/site). The acute treatment with á-tocopherol had no effect in the locomotor activity of animals. In addition, the chronic treatment (4 weeks) with á-tocopherol at the dose of 10 mg/kg reduced the immobility time in the FST, without causing any alteration in the the locomotor activity of animals in the open-field test. Considering the well-known role of vitamin E as an antioxidant, the effect of chronic treatment with á-tocopherol in the glutathione (GSH) antioxidant system was investigated. The chronic treatment with á-tocoferol (10 mg/kg) increased the GSH levels in the hippocampus and in the prefrontal cortex. Moreover, the treatment with á-tocopherol increased the glutathione peroxidase and glutathione reductase activity in the hippocampus (10 mg/kg) and in the prefrontal cortex (10-100 mg/kg). Additionally, this study investigated the involvement of the monoaminergic (serotonergic and noradrenergic) and glutamatergic systems, and of the L-arginine-NO pathway, in the antidepressant-like effect of á-tocopherol in the FST. The anti-immobility effect of á-tocopherol (100 mg/kg, p.o.) was prevented by the pre-treatment of mice with PCPA (100 mg/kg, i.p., four consecutive days), prazosin (1 mg/kg, i.p.), yohimbine (1 mg/kg, i.p.), NMDA (0.1 pmol/site, i.c.v.), D-serine (30 ìg/site, i.c.v.), L-arginine (750 mg/kg, i.p.), SNAP (25 ìg/site, i.c.v) and sildenafil (5 mg/kg, i.p.), but not with propranolol (2 mg/kg, i.p.). In addition, a sub-effective dose of á-tocopherol (10 mg/kg, p.o.) produced a synergistic antidepressant-like effect with WAY100635 (0,1 mg/kg, s.c.), pindolol (32 mg/kg, i.p.), fluoxetine (10 mg/kg, p.o.), phenylephrine (5 mg/kg, i.p.), clonidine (0,06 mg/kg, i.p.), desipramine (8 mg/kg, p.o.), MK-801 (0.001 mg/kg, i.p.), L-NNA (0.3 mg/kg, i.p.), methylene blue (18 mg/kg, i.p.) and ODQ (30 pmol/site, i.c.v.). This study showed that acute and chronic treatment with á-tocopherol produces a specific antidepressant-like effect in animal models of depression. Our results also suggest that the chronic treatment with á-tocopherol improves the antioxidant defences in the hippocampus and in the prefrontal cortex of mice. Moreover, the effect of the acute administration of á-tocopherol in the FST seems to be mediated, at least in part, by an interaction with serotonergic (through 5-HT1A receptors) and noradrenergic (through á1 e á2-adrenoceptors) systems and by the inhibition of NMDA receptors and of NO and cGMP synthesis.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufsc.br:123456789/92948 |
| Date | January 2009 |
| Creators | Lobato, Kelly Ribas |
| Contributors | Universidade Federal de Santa Catarina, Rodrigues, Ana Lucia Severo |
| Publisher | Florianópolis, SC |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | 108 f.| il., grafs. |
| Source | reponame:Repositório Institucional da UFSC, instname:Universidade Federal de Santa Catarina, instacron:UFSC |
| Rights | info:eu-repo/semantics/openAccess |
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