Metabolomic identification of biochemical changes induced by fluoxetine and imipramine in a chronic mild stress mouse model of depression.
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.
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Jing
J
Zhao
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Yang-Hee
YH
Jung
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Choon-Gon
CG
Jang
Gachon Institute of Pharmaceutical Sciences,College of Pharmacy, Gachon University, Incheon 406-799, Republic of Korea.
Kwang-Hoon
KH
Chun
College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
Sung Won
SW
Kwon
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Jeongmi
J
Lee
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage; D002908:Chronic Disease; D003863:Depression / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007099:Imipramine / Q000008:administration & dosage*; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D020543:Proteome / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D020543:Proteome; D007099:Imipramine