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目的:探讨母源性氟西汀暴露对雌性子代大鼠下丘脑垂体肾上腺(hypothalamic pituitary adrenal，HPA)轴及学习记忆功能的影响。方法:孕鼠用随机数字表法分为处理组和对照组，分别于孕11～20 d给予10 mg/kg的氟西汀和等量的生理盐水。取两组的雌仔鼠各10只，于出生后12周分别行旷场实验、电迷宫实验和物体识别实验，测血浆促肾上腺皮质激素(adrenocorticotrophic hormone，ACTH)和皮质酮(corticosterone，CORT)浓度。然后给予21 d不可预见性慢性应激(Unpredictable chronic stress，UCS)，并再次做上述实验。最后处死大鼠，取下丘脑组织，测定促肾上腺皮质激素释放激素(corticotropin releasing hormone，CRH)和精氨酸加压素(arginine vasopressin，AVP)的mRNA表达。采用SPSS 19.0进行描述和n t检验。n 结果:UCS前，两组大鼠的各检测指标均差异无统计学意义(均n P>0.05)。UCS后，两组大鼠的水平运动、垂直运动较处理前均明显减少，且处理组大鼠的水平运动[(37.2±7.2)次，(50.8±8.5)次，n t＝4.73，n P<0.01]和垂直运动[(10.6±2.0)次，(15.2±5.1)次，n t＝2.93，n P<0.05]均低于对照组；两组大鼠的正确反应次数均明显减少，总反应时间明显延长；且处理组大鼠的正确反应次数明显少于对照组[(3.4±1.3)次，(4.5±0.9)次，n t＝2.36，n P<0.05]；处理组大鼠的物体辨别指数显著下降，且低于对照组[(0.11±0.04)，(0.16±0.05)，n t＝2.28，n P<0.05]。UCS前后，处理组大鼠的ACTH变化率[(61.13±26.08)%，(29.83±12.73)%，n t＝3.67，n P<0.01]和CORT变化率[(105.71±18.39)%，(74.15±39.24)%，n t＝2.34，n P<0.05]均明显高于对照组，且下丘脑CRH的mRNA表达明显高于对照组(n t＝4.15，n P0.05). After UCS, the horizontal movement and vertical movement of the rats in the two groups were significantly reduced compared with that before treatment, and the horizontal movement of the rats in the treatment group ((37.2±7.2)n vs (50.8±8.5), n t=4.73, n P<0.01) and vertical movement ((10.6±2.0)n vs (15.2±5.1), n t=2.93, n P<0.05) were lower than those in the control group.The correct reaction times decreased and the total reaction time increased in the two groups.While the correct response times of the treatment group were significantly lower than that of the control group (3.4±1.5)n vs (4.5±0.9), n t=2.36, n P<0.05). The object recognition index of the rats in the treatment group decreased significantly compared with the control group ((0.11±0.04)n vs (0.16±0.05), n t=2.28, n P<0.05). Before and after UCS, the change rate of ACTH ((61.13±26.08)%n vs (29.83±12.73)%, n t=3.67, n P<0.01) and CORT ((105.71±18.39)%n vs (74.15±39.24)%, n t=2.34, n P<0.05) in the treated group was significantly higher than that in the control group, and the mRNA expression of CRH in hypothalamus was significantly higher than that in the control group (n t=4.15, n P<0.01).n Conclusion:No significant damage is found to the HPA axis as well as learning and memory function of female offspring rats after exposure to fluoxetine in pregnancy, but the susceptibility of HPA axis as well as learning and memory function is increased under chronic stress.