Abstract: Objective To evaluate the effects of Caulis Sinomenii and sinomenine on conditioned place preference(CPP)induced by morphine and brain histamine level in mice.Methods Sixty mice were randomized into 6 equal groups and morphine(Mor)was injected subcutaneously(9 mg/kg)for 6 consecutive days to induce CPP using a shuttle box.Since the 4th day of training,the mice in 5 of the groups were treated for 3 consecutive days with Caulis Sinomenii(10 g/kg),sinomenine(60 mg/kg),diphenhydramine(30 mg/kg),CP48/80(5 mg/kg)and L-histidine(750 mg/kg)in addition to morphine(9 mg/kg)treatment,respectively,leaving the other group with exclusive morphine treatment.Another 10 mice received saline injection to serve as saline control group.The content of histamine(HA)in the mouse brain was measured by fluorospectrophotometry.Results In morphine group,the mice showed significantly extended stay in morphine-paired compartment whose HA content in the brain was markedly increased(P<0.01).Treatment with Caulis Sinomenii and sinomenine resulted in significantly reduced time of stay in morphine-paired compartment and brain HA level(P<0.01).Conclusion CPP induced by morphine in mice is associated with increased HA level in the brain.Caulis Sinomenii and sinomenine can suppress the acquisition of place preference induced by morphine and modulate HA level in the central nervous system in morphine-dependent mice.