In this study,we examined the effects of electroacupuncture on phosphodiesterase 4D (PDE4D) and brain-derived neuro-trophic factor (BDNF) expression in rats with chronic stress-induced depression.We investigated the biological mechanism by which electroacupuncture promotes hippocampal nerve regeneration and treats depression.Thirty-two Sprague-Dawley rats were randomly divided into blank control,model,electroacupuncture and fluoxetine groups.Rat models of depression were established by chronic unpredictable stress stimulation in combination with 21 days of solitary confinement in the model,electroacupuncture,and fluoxetine groups.Rats in the electroacupuncture group received electroacupuncture at Baihui and Yintang acupoints for 1 hour before stress stimulation,once per day.The insertion depth was 0.5-1 cm;stimu-lation frequency was 2 Hz;and current intensity was designated as slight trembling of the rats head.The needle was left in place for 20 minutes for each manipulation.Rats in the fluoxetine group received intragastric administration of fluoxetine (prepared with physiological saline,1 mg/mL,2 mg/kg) 1 hour before stress stimulation,once a day.The open field test,performed on day 22,showed that the number of squares crossed and the frequency of rearing by the rats in the model group were significantly reduced from that in the blank control group (P < 0.01).This indicated that rat exploring behaviors and athletic activity were reduced,suggesting depression was successfully induced.The number of squares crossed and the number of rears by the rats in the fluoxetine and electroacupuncture groups were significantly greater than in the fluoxetine and model group (P < 0.01).This suggests that electroacupuncture can reduce the depressive behaviors in rats with chronic stress-induced depression.Quantitative reverse transcription-polymerase chain reaction results obtained on day 22 showed that hippocampal PDE4D mRNA expression in the model group was significantly higher than in the blank control group (P < 0.01).However,hippocampal PDE4D mRNA expression in the electroacupuncture group was significantly lower than in the model group (P < 0.01).There was no significant difference in hippocampal PDE4D mRNA expression between the fluoxetine and the blank control groups.Western blot analysis on day 22 showed that BDNF protein expression in the model group was significantly lower than in the blank control group (P < 0.05).BDNF protein expression in the electroacupunc-ture group was significantly higher than in the model group (P < 0.05).There was no significant difference between the electroacupuncture and blank control groups (P > 0.05).These findings suggest that BDNF expression was decreased in the hippocampus of rats subjected to chronic stress stimulation in combination with solitary confinement,and that electroacu-puncture can reverse this change.Electroacupuncture can downregulate PDE4D expression and upregulate BDNF expression in downstreaming targets,promoting hippocampal nerve regeneration and thereby preventing depression.