Hange-koboku-to, a Kampo medicine, modulates cerebral levels of 5-HT (5-hydroxytryptamine), NA (noradrenaline) and DA (dopamine) in mice

Cerebral monoamine systems play important pathogenic roles in various psychiatric and neurologic diseases, such as depression, anxiety and swallowing disturbance. Hange-koboku-to, a Kampo (Japanese herbal) medicine, has been successfully used for the treatment of these disorders. To elucidate the mechanisms underlying its clinical efficacy for these disorders, the effects of Hange-koboku-to (500 mg/kg, p.o.) on the cerebral monoamine systems were examined. Regional levels of 5-HT (5-hydroxytryptamine), NA (noradrenaline), DA (dopamine) and their metabolites in mouse brain were measured using a high-performance liquid chromatography system. Hange-koboku-to increased the 5-HT and NA levels and decreased 5-HIAA (5-hydroxyindole-3-acetic acid), thus decreasing 5-HT and NA turnover (metabolites/monoamine ratio) in the hypothalamus. The levels of DA, DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (4-hydroxy-3-methoxy-phenylacetic acid) were all increased, resulting in a decreased DA turnover in the striatum. Since decreased 5-HT turnover has been observed after administration of various antidepressants, Hange-koboku-to-mediated reduction of 5-HT turnover may be related to the clinical efficacy of this Kampo medicine on certain psychiatric disorders. Furthermore, the beneficial therapeutic effects of Hange-koboku-to on swallowing disturbance may be related to the increased cerebral DA level brought about by this Kampo medicine.