Program

PO2-12-12

Effects of the traditional Japanese kampo medicine yokukansan on the ethanol-withdrawal in ethanol-dependent mice

[Speaker] Hideaki Kato:1
[Co-author] Minoru Tsuji:1, Kazuya Miyagawa:1, Hiroshi Takeda:1
1:Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, Japan

Yokukansan (YKS) is the traditional Japanese kampo medicine administrated to patients who show symptoms such as nervousness, short-tempered behavior, irritability, sleeplessness, eyelid twitching, and limb shaking. YKS contains a dried extract of the following mixed crude drugs: Atractylodes lancea rhizome, Poria sclerotium, Cnidium rhizome, Uncaria hook, Japanese angelica root, Bupleurum root, Glycyrrhiza and inactive ingredients (lactose hydrate and magnesium stearate). The present study was designed to ascertain the effects of chronic administration of YKS on the ethanol-withdrawal in ethanol-dependent mice. Mice were chronically treated with 3% ethanol according to liquid diet method for 14 days (day 0-14) to establish the ethanol dependent model. In the same term, mice were administered YKS (500 and 1000 mg/kg, p.o.) once a day (day 0-13). Withdrawal was induced by substituting normal liquid diet (0% ethanol-containing liquid diet) for ethanol-containing liquid diet on day 14 following ethanol treatment. The ethanol plus water-treated group showed a marked increase in the intake of normal liquid diet on day 15, which is considered to be trying to avoid an unpleasant ethanol-withdrawal symptom, during ethanol withdrawal. A significant decrease in the intake of normal liquid diet was observed in ethanol plus YKS-treated groups. In addition, after the discontinuation of chronic ethanol treatment, mice revealed several withdrawal signs such as piloerection and tremor. A significant decrease in the withdrawal score was observed in ethanol plus YKS-treated groups. Especially, the weak or severe tremor was significant decreased in ethanol plus YKS-treated groups. These results suggest that treatment of chronic YKS may attenuate the development of ethanol dependence. Additional neurochemical and/or molecular biological experiments based on the present behavioral findings should help us explain the processes that underlie the improvement of ethanol-withdrawal symptom. Considering its availability and advantages, YKS may be useful for alcoholism.
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