title: Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration.
abstract: Current evidences support inflammation, oxidative and nitrogen stress, as well as brain-derived neurotrophic factor (BDNF) signaling mechanisms as important in depression pathophysiology. Tetracycline antibiotics have anti-inflammatory and antioxidant properties. Preliminary evidence indicates that minocycline has antidepressant properties. Doxycycline (DOXY) has favorable pharmacokinetic and safety profiles when compared to other tetracycline congeners. The antidepressant activity of DOXY has not been adequately investigated. This study evaluated the effects of DOXY (25 and 50 mg/kg, i.p.) on LPS-induced (0.5 mg/kg, i.p.) depressive-like behavior. Doxycycline was administered 30 min before LPS (pre-LPS) or 1.5 and 23.5 h following LPS (post-LPS) administration in mice. LPS-treated animals presented an increase in immobility time in the forced swimming test (FST) when compared to controls 24 h after endotoxin administration. Similarly to imipramine (IMI-10 mg/kg, i.p.), DOXY at both doses prevented and reversed LPS-induced alterations in the FST. IL-1β content was increased 24 h after LPS administration in striatum, hippocampus and prefrontal cortex. IMI and DOXY prevented and reversed LPS-induced increase in IL-1β. IMI and DOXY also prevented and reversed LPS-induced alterations in nitrite content and oxidative stress parameters (lipid peroxidation and reduced glutathione levels). Both DOXY and IMI prevented LPS-induced decrease in hippocampal BDNF levels. Taken together, our results demonstrate that DOXY is comparable to IMI in effectively ameliorate LPS-induced depressive-like behavior, providing a rationale for testing DOXY's antidepressant efficacy in humans.
authors.affiliation: Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil.
authors.forename: Bruna Stefânia Ferreira
authors.initials: BS
authors.lastname: Mello
authors.forename: Aline Santos
authors.initials: AS
authors.lastname: Monte
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
authors.forename: Joanna K
authors.initials: JK
authors.lastname: Soczynska
authors.forename: Charllyany Sabino
authors.initials: CS
authors.lastname: Custódio
authors.forename: Rafaela Carneiro
authors.initials: RC
authors.lastname: Cordeiro
authors.forename: João Henrique
authors.initials: JH
authors.lastname: Chaves
authors.forename: Silvânia Maria Mendes
authors.initials: SM
authors.lastname: Vasconcelos
authors.forename: Hélio Vitoriano
authors.initials: HV
authors.lastname: Nobre
authors.forename: Francisca Cléa
authors.initials: FC
authors.lastname: Florenço de Sousa
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Hyphantis
authors.forename: André Férrer
authors.initials: AF
authors.lastname: Carvalho
authors.forename: Danielle Silveira
authors.initials: DS
authors.lastname: Macêdo
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003863:Depression / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000627:therapeutic use*; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D009573:Nitrites / Q000378:metabolism; D018709:Statistics, Nonparametric; D013550:Swimming / Q000523:psychology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D005978:Glutathione; D004318:Doxycycline
keywords: Depression; Doxycycline; Lipopolysaccharide; Neuroinflammation; Oxidative stress