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Study M142

Study name

Zhou WJ 2015

Title

Peripheral indoleamine 2,3-dioxygenase 1 is required for comorbid depression-like behavior but does not contribute to neuropathic pain in mice

Overall design

Chronic pain frequently co-occurs with major depressive disorder but the mechanisms are poorly understood. The authors investigated the contribution of indoleamine 2,3-dioxygenase-1 (IDO1), a rate-limiting enzyme in the conversion of tryptophan to neurotoxic metabolites, to this comorbidity using the spared nerve injury (SNI) model of neuropathic pain in mice. SNI resulted in unilateral mechanical allodynia, reduced social interaction, and increased immobility in the forced swim test without changes in locomotor activity. Assessment of brain and plasma metabolites was conducted using HPLC-MS. Mice were divided into 2 groups: (1) control group (sham surgery), and (2) SNI group (spared nerve injury model of neuropathic pain). For SNI surgery, the sural common peroneal and tibial branches of the left sciatic nerve were exposed under isoflurane anesthesia. The tibial and common peroneal nerves were transected. The sural nerve was kept intact. Forced swim test was performed on day 7 after SNI surgery. On day 8, mice were sacrificed for tissue collection.

Study Type

Type1;

Data available

Unavailable

Organism

Mouse; C57/BL6J mouse;

Categories of depression

Animal model; Other animal model; Other animal model;

Criteria for depression

Forced swimming test

Sample size

15

Tissue

Peripheral; Blood; Plasma;

Central; Brain; Hippocampus;

Central; Brain; Frontal cortex;

Platform

MS-based; LC-MS: Waters Acquity HPLC system with Waters Quattro Premier XE triple quadrupole mass spectrometer;

PMID

25637485

DOI

10.1016/j.bbi.2015.01.013

Citation

Zhou W, Dantzer R, Budac DP, et al. Peripheral indoleamine 2,3-dioxygenase 1 is required for comorbid depression-like behavior but does not contribute to neuropathic pain in mice. Brain Behav Immun 2015; 46:147-53.

Metabolite

L-Kynurenine;

Kynurenine/Tryptophan ratio;