Metabolomic identification of biochemical changes induced by fluoxetine and imipramine in a chronic mild stress mouse model of depression

Jing Zhao, Yang Hee Jung, Choon Gon Jang, Kwang Hoon Chun, Sung Won Kwon, Jeongmi Lee

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Metabolomics was applied to a C57BL/6N mouse model of chronic unpredictable mild stress (CMS). Such mice were treated with two antidepressants from different categories: fluoxetine and imipramine. Metabolic profiling of the hippocampus was performed using gas chromatography-mass spectrometry analysis on samples prepared under optimized conditions, followed by principal component analysis, partial least squares-discriminant analysis, and pair-wise orthogonal projections to latent structures discriminant analyses. Body weight measurement and behavior tests including an open field test and the forced swimming test were completed with the mice as a measure of the phenotypes of depression and antidepressive effects. As a result, 23 metabolites that had been differentially expressed among the control, CMS, and antidepressant-treated groups demonstrated that amino acid metabolism, energy metabolism, adenosine receptors, and neurotransmitters are commonly perturbed by drug treatment. Potential predictive markers for treatment effect were identified: myo-inositol for fluoxetine and lysine and oleic acid for imipramine. Collectively, the current study provides insights into the molecular mechanisms of the antidepressant effects of two widely used medications.

Original languageEnglish (US)
Article number8890
JournalScientific Reports
Volume5
DOIs
StatePublished - 2015

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Metabolomics
Imipramine
Fluoxetine
Antidepressive Agents
Discriminant Analysis
Depression
Purinergic P1 Receptors
Inositol
Oleic Acid
Principal Component Analysis
Least-Squares Analysis
Inbred C57BL Mouse
Gas Chromatography-Mass Spectrometry
Energy Metabolism
Lysine
Neurotransmitter Agents
Hippocampus
Body Weight
Phenotype
Amino Acids

ASJC Scopus subject areas

  • General

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Metabolomic identification of biochemical changes induced by fluoxetine and imipramine in a chronic mild stress mouse model of depression. / Zhao, Jing; Jung, Yang Hee; Jang, Choon Gon; Chun, Kwang Hoon; Kwon, Sung Won; Lee, Jeongmi.

In: Scientific Reports, Vol. 5, 8890, 2015.

Research output: Contribution to journalArticle

Zhao, Jing ; Jung, Yang Hee ; Jang, Choon Gon ; Chun, Kwang Hoon ; Kwon, Sung Won ; Lee, Jeongmi. / Metabolomic identification of biochemical changes induced by fluoxetine and imipramine in a chronic mild stress mouse model of depression. In: Scientific Reports. 2015 ; Vol. 5.
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