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Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration
- Source :
- Journal of Psychiatric Research. 47:1521-1529
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
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.
- Subjects :
- Lipopolysaccharides
Male
Interleukin-1beta
Pharmacology
medicine.disease_cause
Thiobarbituric Acid Reactive Substances
Imipramine
Statistics, Nonparametric
Lipid peroxidation
Mice
chemistry.chemical_compound
Pharmacokinetics
medicine
Animals
Nitrites
Swimming
Biological Psychiatry
Doxycycline
Dose-Response Relationship, Drug
Depression
Tumor Necrosis Factor-alpha
business.industry
Brain-Derived Neurotrophic Factor
Brain
Minocycline
Glutathione
Antidepressive Agents
Disease Models, Animal
Psychiatry and Mental health
Gene Expression Regulation
chemistry
Exploratory Behavior
lipids (amino acids, peptides, and proteins)
business
Oxidative stress
medicine.drug
Behavioural despair test
Subjects
Details
- ISSN :
- 00223956
- Volume :
- 47
- Database :
- OpenAIRE
- Journal :
- Journal of Psychiatric Research
- Accession number :
- edsair.doi.dedup.....a2dfc78c3fa02adc6a4ccce7a86db2f1