Effects of yokukansan and donepezil on learning disturbance and aggressiveness induced by intracerebroventricular injection of amyloid β protein in mice.

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.