Chronic imipramine treatment differentially alters the brain and plasma amino acid metabolism in Wistar and Wistar Kyoto rats

Mao Nagasawa, Tsuyoshi Otsuka, Shinobu Yasuo, Mitsuhiro Furuse

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9 Citations (Scopus)

Abstract

In the present study, the amino acids which have the possibility for the therapeutic efficacy of imipramine were explored and compared between Wistar Kyoto rats, an animal model of depression, and Wistar rats as a normal model. The antidepressant-like effect caused by chronic imipramine treatment was confirmed by decreased immobility in the forced swimming test. Chronic imipramine administration altered the amino acid dynamics in the brain. In the striatum, the concentrations of asparagine, glutamine and methionine were significantly increased by chronic imipramine administration. In the thalamus and hypothalamus, chronic imipramine administration significantly decreased the valine concentration. On the other hand, no amino acid was altered by chronic imipramine administration in the hippocampus, brain stem and cerebellum. In addition, lower concentration of asparagine in the prefrontal cortex of WKY rats was improved by chronic imipramine administration. This amelioration only in WKY rats may be a specific effect of chronic imipramine administration under the depressive state. In conclusion, chronic imipramine administration altered the several amino acid dynamics in the brain. Modification of the amino acid metabolism in the brain may provide a new strategy in the development of therapeutic treatment of major depression.

Original languageEnglish
Pages (from-to)127-135
Number of pages9
JournalEuropean Journal of Pharmacology
Volume762
DOIs
Publication statusPublished - Jun 3 2015

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Inbred WKY Rats
Imipramine
Amino Acids
Brain
Asparagine
Valine
Prefrontal Cortex
Glutamine
Thalamus
Methionine
Cerebellum
Antidepressive Agents
Hypothalamus
Brain Stem
Wistar Rats
Hippocampus
Animal Models

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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abstract = "In the present study, the amino acids which have the possibility for the therapeutic efficacy of imipramine were explored and compared between Wistar Kyoto rats, an animal model of depression, and Wistar rats as a normal model. The antidepressant-like effect caused by chronic imipramine treatment was confirmed by decreased immobility in the forced swimming test. Chronic imipramine administration altered the amino acid dynamics in the brain. In the striatum, the concentrations of asparagine, glutamine and methionine were significantly increased by chronic imipramine administration. In the thalamus and hypothalamus, chronic imipramine administration significantly decreased the valine concentration. On the other hand, no amino acid was altered by chronic imipramine administration in the hippocampus, brain stem and cerebellum. In addition, lower concentration of asparagine in the prefrontal cortex of WKY rats was improved by chronic imipramine administration. This amelioration only in WKY rats may be a specific effect of chronic imipramine administration under the depressive state. In conclusion, chronic imipramine administration altered the several amino acid dynamics in the brain. Modification of the amino acid metabolism in the brain may provide a new strategy in the development of therapeutic treatment of major depression.",
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AB - In the present study, the amino acids which have the possibility for the therapeutic efficacy of imipramine were explored and compared between Wistar Kyoto rats, an animal model of depression, and Wistar rats as a normal model. The antidepressant-like effect caused by chronic imipramine treatment was confirmed by decreased immobility in the forced swimming test. Chronic imipramine administration altered the amino acid dynamics in the brain. In the striatum, the concentrations of asparagine, glutamine and methionine were significantly increased by chronic imipramine administration. In the thalamus and hypothalamus, chronic imipramine administration significantly decreased the valine concentration. On the other hand, no amino acid was altered by chronic imipramine administration in the hippocampus, brain stem and cerebellum. In addition, lower concentration of asparagine in the prefrontal cortex of WKY rats was improved by chronic imipramine administration. This amelioration only in WKY rats may be a specific effect of chronic imipramine administration under the depressive state. In conclusion, chronic imipramine administration altered the several amino acid dynamics in the brain. Modification of the amino acid metabolism in the brain may provide a new strategy in the development of therapeutic treatment of major depression.

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