Objective：To study the effect of cocaine- and amphetamine-regulated transcript (CART) protein vaccine on morphine analgesia and tolerance.Methods: The expression plasmid pGEX-4T3-CART was constructed by gene cloning.The CART protein was purified by glutathione s-transferase(GST)-affinity chromatography.The experiment included 6 groups:blank control,normal saline (NS),GST+Freund’s adjuvant,and CART protein vaccine (5 μg,10 μg and 20 μg) groups.After immunization for twice,all groups were tested in hot plate.Morphine analgesia effect was evaluated through s.c. injection with 6 mg/kg morphine solution,calculated by MPE%.Then morphine tolerance model was established,and the tolerance to morphine was tested by s.c. injection with 6 mg/kg morphine 12 h after the last injection.Results: CART vaccine itself had no pronounced effect on the pain threshold (P>0.05).CART vaccine at 10 μg significantly depressed the analgesic effect of morphine analgesia (P<0.05).Compared with NS group,vaccine groups showed a potential antagonizing tolerance effect,especially in the 10 μg group,with the MPE% significantly increased(P<0.05).Conclusion: CART vaccine itself has no influence on the pain response; however,it can impair the analgesia effect of morphine and can antagonize the analgesia tolerance to morphine.