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Abstract
The relationship between antidepressants and monoamine concentrations in the brain has been well investigated, but few studies have investigated the relationship between antidepressants and amino acid concentrations in the brain. The purpose of the present study was therefore to investigate the effect of the chronic antidepressant imipramine on amino acid and monoamine concentrations in the mouse brain and plasma. Chronic imipramine treatment decreased the concentration of 5-hydroxyindoleaceticacid/5-hydroxytryptamine in the cerebral cortex and increased that of norepinephrine (NE) in the hippocampus. Since these changes were conspicuous effects of the antidepressant, we concluded that imipramine acts on the central nervous system. No change in amino acid concentrations in plasma was induced by chronic imipramine treatment, but several changes were confirmed in the cerebral cortex, the hypothalamus and the hippocampus. Chronic imipramine treatment caused increases in l-methionine, l-tyrosine, and l-lysine in the cerebral cortex, and an increase in l-aspartate in the hypothalamus. Contrary to this, the concentrations of l-aspartate, l-serine, l-asparagine, glycine, l-glutamine, gamma-aminobutyric acid, l-threonine, l-arginine, l-proline, l-valine, and l-methionine in the hippocampus were decreased by chronic imipramine treatment. The present results demonstrate that the metabolism of several amino acids in the brain, but not of those in plasma, was altered by chronic imipramine treatment. The findings in the present study may help to further elucidate the relationship between amino acids and the effects and side effects of antidepressants.
Acknowledgments
The authors are grateful to Dr M.A. Cline and Dr B.A. Newmyer, Radford University, USA, for their reading of the manuscript, and the staff and students of the Laboratory of Chemistry and Technology of Animal Products in Kyushu University for their assistance in the amino acid analysis.