Cited by 195Tryptophan and brain disordersTreatment of Major DepressionStress Responses and Cortisol

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Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration

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Ferreira Mello, Bruna Stefânia, Monte, Aline Santos, McIntyre, Roger S., Soczynska, Joanna K., Custódio, Charllyany Sabino, Cordeiro, Rafaela Carneiro, Chaves, João Henrique, Mendes Vasconcelos, Silvânia Maria, Nobre Júnior, Hélio Vitoriano, Florenço de Sousa, Francisca Cléa, Hyphantis, Thomas N., Carvalho, André Férrer, Macêdo, Danielle Silveira·2013·Journal of Psychiatric Research

DOI 10.1016/j.jpsychires.2013.06.008

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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.

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Authors: Ferreira Mello, B. S., Monte, A. S., McIntyre, R. S., Soczynska, J. K., Custódio, C. S., Cordeiro, R. C., Chaves, J. H., Mendes Vasconcelos, S. M., Nobre Júnior, H. V., Florenço de Sousa, F. C., Hyphantis, T. N., Carvalho, A. F., & Macêdo, D. S.
Affiliations: Universidade Federal do Ceará (BR)
University Health Network (CA)
University of Toronto (CA)
University of Ioannina (GR)
Corresponding author: Macêdo, Danielle Silveira
ORCID: Monte, Aline Santos
McIntyre, Roger S.
Soczynska, Joanna K.
Cordeiro, Rafaela Carneiro
Chaves, João Henrique
Hyphantis, Thomas N.
Macêdo, Danielle Silveira
Venue: Journal of Psychiatric Research
Publisher: Elsevier BV
Published: 2013-10
Volume: 47
Issue: 10
Pages: 1521-1529
ISSN: 0022-3956 (ISSN-L)
DOI: 10.1016/j.jpsychires.2013.06.008
OpenAlex: W2081306572
Cited by: 195
References: 99
Citations by year: 2026: 6 · 2025: 9 · 2024: 10 · 2023: 12 · 2022: 16 · 2021: 22 · 2020: 20 · 2019: 20 · 2018: 19 · 2017: 18 · 2016: 13 · 2015: 15 · 2014: 15
FWCI: 4.85
Type: journal article
Language: en
Open access: green
www.repositorio.ufc.br
Licence: other-oa
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Psychiatric Research (publishedVersion)
PubMed (publishedVersion)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
Funders: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: doxycycline, antidepressant effects, depression-like behavior, lipopolysaccharide, neuroinflammation, brain-derived neurotrophic factor, IL-1β, oxidative stress, lipid peroxidation, glutathione, imipramine, tetracycline antibiotics, forced swim test, hippocampus, prefrontal cortex, striatum
MeSH terms: Animals, Antidepressive Agents, Brain, Depression, Disease Models, Animal, Dose-Response Relationship, Drug, Doxycycline, Exploratory Behavior, Gene Expression Regulation, Glutathione, Lipopolysaccharides, Male, Nitrites, Swimming, Tumor Necrosis Factor-alpha, Thiobarbituric Acid Reactive Substances, Statistics, Nonparametric, Brain-Derived Neurotrophic Factor, Mice, Interleukin-1beta

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Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration

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