The impact of chronic imipramine treatment on amino acid concentrations in the hippocampus of mice.

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.

Orally administered L-ornithine elevates brain L-ornithine levels and has an anxiolytic-like effect in mice.

Intracerebroventricular injection of L-ornithine has demonstrated sedative and hypnotic effects in neonatal chicks exposed to acute stressful conditions. However, whether orally administered L-ornithine can reduce acute mental stress remains to be defined. To clarify the nutritional importance of L-ornithine in controlling the stress response, in Experiment 1 we first investigated whether orally administered L-ornithine can be transported into the brain of mice. Mice were orally administered L-ornithine (3 mmol/water 10 ml/kg, per os). L-Ornithine levels were significantly elevated in the cerebral cortex and hippocampus at 30 and 60 minutes post-administration. In Experiment 2, the effect of orally administered L-ornithine (0, 0.1875, 0.75 and 3 mmol/water 10 ml/kg, per os) on anxiety-like behavior in mice exposed to the elevated plus-maze test was examined at 30 minutes post-administration. There was a significant increase in the percentage of time spent and entries in the open arms in the group receiving 0.75 mmol of L-ornithine compared to the control group. Furthermore, locomotion activity in a novel environment was not significantly changed between the control group and 0.75 mmol of L-ornithine group in Experiment 3. Therefore, it appears that orally administrated L-ornithine is bioavailable to the rodent brain and reduces anxiety-like behavior as demonstrated by the elevated plus-maze test.