Chronic treatment with the IDO1 inhibitor 1-methyl-D-tryptophan minimizes the behavioural and biochemical abnormalities induced by unpredictable chronic mild stress in mice - Comparison with fluoxetine

Anthony Laugeray*, Jean Marie Launay, Jacques Callebert, Oguz Mutlu, Gilles J. Guillemin, Catherine Belzung, Pascal R. Barone

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)
19 Downloads (Pure)

Abstract

We demonstrated that confronting mice to the Unpredictable Chronic Mild Stress (UCMS) procedure - a validated model of stress-induced depression - results in behavioural alterations and biochemical changes in the kynurenine pathway (KP), suspected to modify the glutamatergic neurotransmission through the imbalance between downstream metabolites such as 3-hydroxykynurenine, quinolinic and kynurenic acids. We showed that daily treatment with the IDO1 inhibitor 1-methyl-D-tryptophan partially rescues UCMS-induced KP alterations as does the antidepressant fluoxetine. More importantly we demonstrated that 1-methyl-D-tryptophan was able to alleviate most of the behavioural changes resulting from UCMS exposure. We also showed that both fluoxetine and 1-methyl-D-tryptophan robustly reduced peripheral levels of proinflammatory cytokines in UCMS mice suggesting that their therapeutic effects might occur through anti-inflammatory processes. KP inhibition might be involved in the positive effects of fluoxetine on mice behaviour and could be a relevant strategy to counteract depressive-like symptoms.

Original languageEnglish
Article numbere0164337
Pages (from-to)1-17
Number of pages17
JournalPLoS ONE
Volume11
Issue number11
DOIs
Publication statusPublished - 9 Nov 2016

Bibliographical note

Copyright the Author(s) 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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