Effects of single and repeated administrations of Toki-shakuyaku-san on the concentrations of brain neurotransmitters in mice.

The amounts of monoamine-related substances (NE, MHPG, DA, DOPAC, HVA, 5-HT, and 5-HIAA and acetylcholine (ACh) in the cerebral cortex, corpus striatum and hippocampus of mice treated orally with a powdered extract of Toki-shakuyaku-san (TSS) were measured using the HPLC-ECD method. Single administration of TSS at 50 mg/kg decreased the content of NE in the hippocampus, but increased the contents of DA, DOPAC and HVA. Single administration of TSS at 50 mg/kg increased the contents of DA and HVA in the cerebral cortex and those of DA, DOPAC and HVA in the hippocampus, but decreased the content of NE. Repeated administration (twice a day, for 14 days) of TSS at 50 mg/kg increased the contents of DA, DOPAC and 5-HIAA in the cerebral cortex, while 500 mg/kg increased the contents of NE, MHPG, DOPAC, 5-HT and 5-HIAA in the cerebral cortex, and the NE and DA in the corpus striatum. With regard to ACh content, single and repeated administrations of TSS at 50 and 500 mg/kg had no influence in the three regions of mouse brain. These results suggest that single administration of TSS stimulates the function of the dopaminergic nervous system in the hippocampus in mice and inhabits the function of the adrenergic nervous system, and that repeated administration of TSS stimulates the function of the adrenergic, dopaminergic and serotonergic nervous systems in the cerebral cortex. TSS, however, did not show any influence on the brain ACh content in mice.