Yokukansan inhibits morphine tolerance and physical dependence in mice: The role of α2A-adrenoceptor

► Yokukansan (YKS) is a traditional Japanese herbal medicine clinically used for BPSD. ► Repeated administration of YKS inhibits morphine tolerance and physical dependence. ► The inhibition is due to prevention of decrease in α2A-AR by its prolonged blockade. ► YKS and its chemical constituents show antagonist activity against α2A-AR. ► The active constituents are responsible for the inhibitory effect of YKS.