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

Zhao J, Jung YH, Jang CG, Chun KH, Kwon SW, Lee J - Sci Rep (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.

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.

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Related in: MedlinePlus

Measurement of total-travelled distance in the open field test at day 0 (a), 7 (b), 14 (c), 21 (d), and 27 (e) of the CMS procedure.** indicates p < 0.01. (Con, control group treated with saline; Cms, CMS group treated with saline; Flu, fluoxetine-treated group; Imi, imipramine-treated group).
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f2: Measurement of total-travelled distance in the open field test at day 0 (a), 7 (b), 14 (c), 21 (d), and 27 (e) of the CMS procedure.** indicates p < 0.01. (Con, control group treated with saline; Cms, CMS group treated with saline; Flu, fluoxetine-treated group; Imi, imipramine-treated group).

Mentions: Locomotor activity was measured weekly during the stress period (day 0, 7, 14, 21, and 27) as total-travelled distance in the OFT to evaluate the stress-related status of the mouse model (Figs. 1 and 2). Mean total-travelled distance of control and drug-treated groups had a tendency to decrease over time during the stress period. However, the total distance of the stressed group with no drug treatment (Cms) generally remained unchanged. As a result, the total-travelled distance of the Cms group was significantly higher than that of the control group at day 21 and day 27 (p < 0.01). At day 21, which was one week after drug treatment, the total distance of the fluoxetine-treated (Flu) group was significantly decreased compared to the Cms group (p < 0.01), while a noticeable, but insignificant difference was observed between the Cms and imipramine-treated (Imi) groups (p = 0.0520) (Fig. 2d). On the last day of the stress period (day 27), the total-travelled distance of the Imi group was reduced to a level close to the control group. In the meantime, travel distance was lower in the Flu than the Cms group, but this difference was not statistically significant at day 27.


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

Zhao J, Jung YH, Jang CG, Chun KH, Kwon SW, Lee J - Sci Rep (2015)

Measurement of total-travelled distance in the open field test at day 0 (a), 7 (b), 14 (c), 21 (d), and 27 (e) of the CMS procedure.** indicates p < 0.01. (Con, control group treated with saline; Cms, CMS group treated with saline; Flu, fluoxetine-treated group; Imi, imipramine-treated group).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352870&req=5

f2: Measurement of total-travelled distance in the open field test at day 0 (a), 7 (b), 14 (c), 21 (d), and 27 (e) of the CMS procedure.** indicates p < 0.01. (Con, control group treated with saline; Cms, CMS group treated with saline; Flu, fluoxetine-treated group; Imi, imipramine-treated group).
Mentions: Locomotor activity was measured weekly during the stress period (day 0, 7, 14, 21, and 27) as total-travelled distance in the OFT to evaluate the stress-related status of the mouse model (Figs. 1 and 2). Mean total-travelled distance of control and drug-treated groups had a tendency to decrease over time during the stress period. However, the total distance of the stressed group with no drug treatment (Cms) generally remained unchanged. As a result, the total-travelled distance of the Cms group was significantly higher than that of the control group at day 21 and day 27 (p < 0.01). At day 21, which was one week after drug treatment, the total distance of the fluoxetine-treated (Flu) group was significantly decreased compared to the Cms group (p < 0.01), while a noticeable, but insignificant difference was observed between the Cms and imipramine-treated (Imi) groups (p = 0.0520) (Fig. 2d). On the last day of the stress period (day 27), the total-travelled distance of the Imi group was reduced to a level close to the control group. In the meantime, travel distance was lower in the Flu than the Cms group, but this difference was not statistically significant at day 27.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.

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.

Show MeSH
Related in: MedlinePlus