Objective:To observe the effect of reward alteration following acupuncture for morphine withdrawal rats on the behavior and neuronal discharges in the medial prefrontal cortex (mPFC). Methods:The Sprague-Dawley (SD) rats were randomly allocated into a model group, a confinement group, an electroacupuncture (EA) group, and a control group. Rats with morphine addiction were made by intraperitoneal injection of naloxone (same dose injection of saline for rats in the control group), followed by a 2-week morphine withdrawal. Acupuncture and confinement were completed during the morphine withdrawal period. Upon withdrawal, the rats received conditioned place preference (CPP) training and open field test. The multi-channel neural signal processor was used in the electrophysiological experiment to measure the neuronal discharges in different subareas of prefrontal cortex in CPP box and aversion box. Results:Rats in the model group and the confinement group spent longer period of time in CPP box than those in the EA group and the control group (allP<0.01); there was no statistically significant difference between the EA group and the control group. The total distances of movement by rats in the model group and the confinement group were longer than those in the EA group and the control group (allP<0.01). The mPFC neuronal discharge frequencies were compared between morphine preference box and aversion box. The mPFC neuronal discharge frequencies in the model group and the confinement group were higher than those in the EA group and the control group (allP<0.05); there was no statistically significant difference between the EA group and the control group. Conclusion:Acupuncture can effectively interfere with the reward alteration following morphine withdrawal, possibly because of its involvement with the mPFC neuronal discharges.