OBJECTIVE To investigates whether AQP4 affects opioid psychological addiction and reveal the mechanisms underlying the role of AQP4 in opioid addiction.METHODS ① In the heroin self-administration experiment, we compared the AQP4 knockout mice with the wild type mice.The process is that train mice to learn heroin self-administration (0.05 mg/kg/infusion) under a fixedratio 1 (FR1) reinforcement schedule.And then, switch the heroin doses with 0.00625, 0.0125, 0.025, 0.05, or 0.1 mg/kg/infusion in a randomized counterbalanced assignment design.At last, all mice underwent extinction and reinstatement test.② In oral sucrose self-administration, the procedures were similar to heroin self-administration, 5% sucrose solution was used for the mice.③ In locomotor activity test, mice were placed in the chamber for 0.5 h of habituation, and then given saline or morphine (5, 10, or 20 mg·kg-1 sc).RESULTS We found that AQP4 deletion had no effect sucrose-taking and sucrose-seeking, but significantly attenuated heroin-taking and heroin-seeking behaviors in heroin self-administration.Besides these, AQP4 deletion had no effect basal level of locomotion, but decreases locomotor-stimulating response to morphine at dose of 10 mg·kg.CONCLUSION Our present findings demonstrate that AQP4 deletion produces attenuated heroin-taking and heroin seeking behaviors.