Changes in 5-hydroxytryptamine and its metabolite, 5-hydroxyindole-acetic acid, levels in the brain of rats administered with methotrexate

During the delayed emesis phase, methotrexate tended to increase 5-hydroxytryptamine (5-HT) levels in midbrain and significantly increased 5-hydroxyindole-acetic acid (5-HIAA), a metabolite of 5-HT, levels in the area postrema and in the cerebral cortex in rats. However, methotrexate did not increase mRNA expression of 5-HT biosynthesis/metabolism enzyme in the area postrema. The increased 5-HIAA levels in the area postrema may result from enhanced intestinal 5-HT synthesis, with 5-HIAA reaching the area postrema via circulation. Additionally, the rise in cortical 5-HIAA levels might reflect stress-related increases in brain tryptophan influx.