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OBJECTIVE Our previous research indicated that AQP4 deficiency potentiated morphine analgesia, attenuated morphine tolerance and physical dependence.The present study investigates whether AQP4 affects opioid psychological addiction and reveal the mechanisms underlying the role of AQP4 in opioid addiction.METHODS 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 fixed-ratio 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 s.c.).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.