PMID- 23835040
OWN - NLM
STAT- MEDLINE
DCOM- 20140404
LR  - 20130813
IS  - 1879-1379 (Electronic)
IS  - 0022-3956 (Linking)
VI  - 47
IP  - 10
DP  - 2013 Oct
TI  - Effects of doxycycline on depressive-like behavior in mice after 
      lipopolysaccharide (LPS) administration.
PG  - 1521-9
LID - S0022-3956(13)00191-X [pii]
LID - 10.1016/j.jpsychires.2013.06.008 [doi]
AB  - 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-1beta 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-1beta. 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.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Mello, Bruna Stefania Ferreira
AU  - Mello BS
AD  - Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty 
      of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil.
FAU - Monte, Aline Santos
AU  - Monte AS
FAU - McIntyre, Roger S
AU  - McIntyre RS
FAU - Soczynska, Joanna K
AU  - Soczynska JK
FAU - Custodio, Charllyany Sabino
AU  - Custodio CS
FAU - Cordeiro, Rafaela Carneiro
AU  - Cordeiro RC
FAU - Chaves, Joao Henrique
AU  - Chaves JH
FAU - Vasconcelos, Silvania Maria Mendes
AU  - Vasconcelos SM
FAU - Nobre, Helio Vitoriano Jr
AU  - Nobre HV Jr
FAU - Florenco de Sousa, Francisca Clea
AU  - Florenco de Sousa FC
FAU - Hyphantis, Thomas N
AU  - Hyphantis TN
FAU - Carvalho, Andre Ferrer
AU  - Carvalho AF
FAU - Macedo, Danielle Silveira
AU  - Macedo DS
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130706
PL  - England
TA  - J Psychiatr Res
JT  - Journal of psychiatric research
JID - 0376331
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nitrites)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - GAN16C9B8O (Glutathione)
RN  - N12000U13O (Doxycycline)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*therapeutic use
MH  - Brain/drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Depression/*chemically induced/*drug therapy/pathology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Doxycycline/*therapeutic use
MH  - Exploratory Behavior/drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Glutathione/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Lipopolysaccharides/*toxicity
MH  - Male
MH  - Mice
MH  - Nitrites/metabolism
MH  - Statistics, Nonparametric
MH  - Swimming/psychology
MH  - Thiobarbituric Acid Reactive Substances/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Depression
OT  - Doxycycline
OT  - Lipopolysaccharide
OT  - Neuroinflammation
OT  - Oxidative stress
EDAT- 2013/07/10 06:00
MHDA- 2014/04/05 06:00
CRDT- 2013/07/10 06:00
PHST- 2013/03/28 00:00 [received]
PHST- 2013/06/01 00:00 [revised]
PHST- 2013/06/14 00:00 [accepted]
PHST- 2013/07/10 06:00 [entrez]
PHST- 2013/07/10 06:00 [pubmed]
PHST- 2014/04/05 06:00 [medline]
AID - S0022-3956(13)00191-X [pii]
AID - 10.1016/j.jpsychires.2013.06.008 [doi]
PST - ppublish
SO  - J Psychiatr Res. 2013 Oct;47(10):1521-9. doi: 10.1016/j.jpsychires.2013.06.008. 
      Epub 2013 Jul 6.