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The effects of yokukansan and donepezil on learning disturbance and aggressiveness were examined in amyloid β protein (Aβ)-injected mice. Intellicage tests showed that both yokukansan and donepezil ameliorated Aβ-induced learning disturbance, but the ameliorating effect of donepezil was not enhanced by concomitant administration of yokukansan. On the other hand, a social interaction test showed that Aβ-induced aggressiveness was ameliorated by yokukansan, but not by donepezil. Co-administration of both drugs also ameliorated aggressiveness, as did yokukansan alone. In vitro binding assays revealed that yokukansan did not bind to choline receptors or transporters. In vitro enzyme assays revealed that yokukansan did not affect choline acetyltransferase activity or inhibit acetylcholinesterase activity, as did donepezil. These results suggest that yokukansan might ameliorate aggressiveness without interfering with the pharmacological efficacy (antidementia effect) of donepezil and also that concomitant administration of yokukansan might be useful for amelioration of aggressiveness, which was not lessened by donepezil. The difference in the efficacies of both drugs may be due to a difference in their pharmacological mechanisms., (Copyright © 2010 John Wiley & Sons, Ltd.)

The effects of yokukansan, a traditional Japanese medicine, on aggressiveness and motor activities were examined in mice after injection of amyloid beta protein (Abeta) into the lateral ventricle of the brain. The results were compared with those of conventional (haloperidol) and atypical (risperidone) antipsychotic medicines. A significant increase in aggressiveness was observed on day 7 after injection of Abeta, and it lasted until day 28. A single oral administration of yokukansan (1.0 g/kg) did not ameliorate the aggressiveness observed on day 7. However, a tendency toward amelioration of the aggressiveness was observed after the administration of yokukansan (0.5 and 1.0 g/kg) for 1 week (days 7-14). The 3 week administration (days 7-28) of yokukansan significantly ameliorated the aggressiveness in a dose-dependent manner without inhibition of motor activity. In contrast, a single administration of intraperitoneal haloperidol (0.03-0.1 mg/kg) or oral risperidone (0.1-0.3 mg/kg) on day 28 significantly reduced aggressiveness in a dose-dependent manner. However, motor activities were significantly suppressed. These results suggest yokukansan reduces aggressiveness without suppressing physical activity., (Copyright 2009 John Wiley & Sons, Ltd.)