Journal
NEUROSCIENCE
Volume 207, Issue -, Pages 124-136Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2012.01.037
Keywords
aggressiveness; geissoschizine methyl ether; serotonin(1A) receptor; sociality; Uncaria hook; yokukansan
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Yokukansan (YKS), a traditional Japanese medicine, is composed of seven kinds of dried herbs. It is widely prescribed in clinical situation for treating psychiatric disorders such as aggressiveness in patients with dementia. We previously demonstrated that YKS and Uncaria hook (UH), which is a constituent herb of YKS, had a partial agonistic effect to 5-HT1A receptors in vitro. However, it has still been unclear whether this in vitro effect is reflected in in vivo, and what the active ingredients are. The purpose of the present study is to find the active ingredient in YKS and to demonstrate the effect in in vivo. In the present study, we first studied the effect of YKS and UH on aggressiveness and sociality in socially isolated mice. YKS and UH ameliorated the isolation-induced increased aggressiveness and decreased sociality, and these ameliorative effects were counteracted by coadministration of 5-HT1A receptor antagonist WAY-100635, or disappeared by eliminating UH from YKS. These results suggest that the effect of YKS is mainly attributed to UH, and the active ingredient is contained in UH. To find the candidate ingredients, we examined competitive binding assay and [S-35] guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) binding assay of seven major alkaloids in UH using Chinese hamster ovary cells expressing 5-HT1A receptors artificially. Only geissoschizine methyl ether (GM) among seven alkaloids potently bound to 5-HT1A receptors and acted as a partial agonist. This in vitro result on GM was further demonstrated in the socially isolated mice. As did YKS and UH, GM ameliorated the isolation-induced increased aggressiveness and decreased sociality, and the effect was counteracted by coadministration of WAY-100635. These lines of results suggest that GM in UH is potent 5-HT1A receptor agonist and a candidate for pharmacological effect of YKS on aggressiveness and sociality in socially isolated mice. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
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