Study M150

Study name

Fischer CW 2015

Title

Interferon-alpha treatment induces depression-like behaviour accompanied by elevated hippocampal quinolinic acid levels in rats

Overall design

The aim of this study was to investigate the effects of IFN-alpha on depression-like behaviour and central metabolites of the tryptophan-kynurenine pathway in rats. Secondly, the modulating effects of an antidepressant (imipramine) and anti-inflammatory drug (celecoxib) on IFN-alpha-induced behavioural and pathophysiological changes in the brain were explored. Eight compounds were measured (tryptophan, 5- hydroxytryptophan, kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid, quinolinic acid and nicotinamide) in right frontal cortex, right hippocampus and hypothalamus tissues using LC-MS. All the rats were divided into the following 4 groups (n = 10 in each group): (1) control group, (2) IFN-alpha group, (3) IFN-alpha + imipramine group (IFN-alpha plus imipramine treatment at the dose of 10 mg/kg), and (4) IFN-alpha + celecoxib group (IFN-alpha plus celecoxib treatment at the dose of 16 mg/kg). IFN-alpha was administered by daily subcutaneous injections at a dose of 6 x 104 IU/kg. Imipramine and celecoxib were administered by food. Depression-like behaviour was assessed on day 7, and the experiment was terminated 24 h after the 7th injection on day 8. IFN-alpha treatment induced depression-like behaviour by increasing immobility in the forced swim test.

Study Type

Type1;

Type2;

Data available

Unavailable

Organism

Rat; Sprague-Dawley rat;

Categories of depression

Animal model; Other animal model; Other animal model;

Criteria for depression

Sucrose preference test, forced swimming test

Sample size

40

Tissue

Central; Brain; Frontal cortex;

Central; Brain; Hippocampus;

Central; Brain; Hypothalamus;

Platform

MS-based; LC-MS: Waters i-Class Acquity UPLC system with Waters Quattro Premier Tandem mass spectrometer;

PMID

26205824

DOI

10.1016/j.bbr.2015.07.015

Citation

Fischer CW, Eskelund A, Budac DP, et al. Interferon-alpha treatment induces depression-like behaviour accompanied by elevated hippocampal quinolinic acid levels in rats. Behav Brain Res 2015; 293:166-72.

Metabolite

L-Tryptophan;

Niacinamide;

Quinolinic acid;