Abstract: Objective To study the behavioral characteristics of memory maintenance and regression in a mouse model of combined learning and memory training with fluoxetine treatment and explore the neural basis for learning and memory in the barrel area of the brain. Methods Twenty-six 16-day-old C57 mice were randomized into two equal groups and were given daily intraperitoneal injection of saline (control) or fluoxetine. The mice were subjected to stimulation of the right whiskers using a multi- sensory stimulation simulator and were given simultaneously olfactory stimulation with butyl acetate. In the initial 10 days of the experiment, the mice were given corresponding drug treatment followed by whisker and olfactory stimulations on a daily basis; from day 11 to day 17, only the drugs were administered without the stimulations; on day 18, both the drugs and stimulations were administered. The daily performance of the mice was recorded and analyzed. In the field potential experiment, the left barrel cortex of the mouse brain was selected to record the frequency of field potential signals in response to whisker stimulation. Results In the behavioral test, the mice treated with fluoxetine showed greater increments of the frequency and angle of whisker deflection than the control mice (P<0.01). Compared with the peak levels that occurred on the 10th day, the swing angle and frequency of the whisker deflection decreased on the 17th day decreased in both groups, and the reduction was more obvious in the control group (P<0.05). During the training on the 18th day, the whisker movement of the mice increased rapidly to the peak level and showed significant differences between the two groups (P<0.05). In the field potential experiment on the 10th and 17th day, the frequencies of field potential signal in response to whisker stimulation was significantly higher in fluoxetine group than in the control group (P<0.05). Conclusion Combined training of the mice results in the formation of combined memory. Fluoxetine can enhance combined learning and memory abilities and prolong such memories in mice by promoting the function of the barrel cortex cells.