Preventive effect of kami-untan-to on performance in the forced swimming test in thiamine-deficient mice: Relationship to functions of catecholaminergic neurons

The kampo (Japanese herbal) medicine "kami-untan-to" (KUT) has been used for a long time in the treatment of neuropsychiatric disorders. We have recently reported that mice put on a thiamine-deficient (TD) diet exhibit a depressive behavior and impairment in avoidance learning after 20 days, and that this impairment was reversed by the chronic administration of KUT. In the present study, we investigated the effect of KUT on the depressive behavior observed in TD mice by using the forced swimming test. Our results show that oral administration of KUT from the 1st day of TD feeding prevented the increased duration of immobility in TD mice. Administration of KUT from the 10th day of TD feeding also had a beneficial effect on depressive behavior. To examine the relationship between the potential effects of KUT on monoaminergic neuronal functions and the depressive behavior observed in TD mice, we measured the immunohistochemical distribution of tyrosine hydroxylase (TH) in the brain using microphotometry. The fluorescence intensity of TH decreased in the limbic cortex and brainstem in TD mice compared with pair-fed mice as the control group, while KUT treatment protected against these decreases. These results suggest that KUT treatment may prevent a sign of depressive behavior, the animal immobility time, induced by TD feeding through a mechanism that involves the decrease of TH in some brain areas of TD mice.