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Effects of zinc and paracetamol on depressive-like behavior of rats induced by lipopolysaccharide

Grant number: 15/02742-0
Support type:Scholarships in Brazil - Master
Effective date (Start): August 01, 2015
Effective date (End): June 30, 2017
Field of knowledge:Biological Sciences - Pharmacology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Thiago Berti Kirsten
Grantee:Danilo Cabral
Home Institution: Vice-Reitoria de Pós-Graduação e Pesquisa. Universidade Paulista (UNIP). São Paulo , SP, Brazil

Abstract

Depression has presenting high prevalence, high relation with unemployment and suicide, as well as requiring long and expensive treatments. Little is known about the etiology of depression, but it seems to include genetic, psychological and pharmacological factors. One hypothesis that has been considered in the genesis of depression is from immune/inflammatory activations. For example, many depressed patients exhibit a chronic increase of pro-inflammatory cytokines levels, and changes in the hypothalamic-pituitary-adrenal axis and in brain-derived neurotrophic factor (BDNF). In this sense, many drugs that interfere with the neuroimmune system have been tested for the depression treatment. Zinc and paracetamol interfere with the immune system, as well as have shown beneficial effects in depression treatment, when administered concurrently to subeffective antidepressants doses. Thus, the objective of this study is to treat rats with zinc and/or paracetamol in an attempt to prevent/ameliorate experimentally induced depressive-like effects, in this case without antidepressants administration. We will induce depressive-like behavior in adult Wistar rats by repeated administration of lipopolysaccharide (LPS, Gram-negative bacteria endotoxin). Rats will receive zinc and/or paracetamol for three consecutive days. First we will evaluate if the sickness behavior induced by LPS will cease, assessing open-field general activity and body weight. We will evaluate anxiety levels by light-dark box test. The depressive-like behavior will be evaluated by the forced swim test. We will also evaluate plasma levels of biomarkers linked to depression, such as BDNF, adrenocorticotropic hormone and tumor necrosis factor alpha, as well as brain analysis (frontal cortex, striatum and midbrain) by immunohistochemistry technique to study neuroinflammation markers (glial protein fibrillary acidic) and dopaminergic system (tyrosine hydroxylase). (AU)