Effects of maternal fluoxetine exposure on hypothalamic pituitary adrenal axis, as well as learning and memory function in female offspring rats after chronic stress

Abstract

Objective To investigate the effects of maternal fluoxetine exposure on hypothalamic pituitary adrenal(HPA) axis and learning and memory function in female offspring rats. Methods Pregnant rats were divided into treatment group and control group by a table of random numbers, which were given fluoxetine (10 mg/kg per day) or the same amount of normal saline at 11-20 days of gestation, respectively.Ten female offspring from each group were selected randomly for open field, electrical maze and object recognition tests at 12 weeks after birth, and the concentrations of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were determined.Then they were given an unpredictable chronic stress (UCS) for 21 days, and the previous experiments were repeated.Finally, rats were sacrificed and the hypothalamus tissues were taken to measure the mRNA expression of corticotropin releasing hormone (CRH) and arginine vasopressin (AVP). SPSS 19.0 was used for data describing and t-test. Results Before UCS, there were no significant differences between the two groups among all the indexes(all P>0.05). 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) vs (50.8±8.5), t=4.73, P<0.01) and vertical movement ((10.6±2.0) vs (15.2±5.1), t=2.93, 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) vs (4.5±0.9), t=2.36, 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) vs (0.16±0.05), t=2.28, P<0.05). Before and after UCS, the change rate of ACTH ((61.13±26.08)% vs (29.83±12.73)%, t=3.67, P<0.01) and CORT ((105.71±18.39)% vs (74.15±39.24)%, t=2.34, 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 (t=4.15, P<0.01). 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. Key words: Fluoxetine; Learning and memory; Hypothalamic-pituitary-adrenal axis; Chronic stress