哺乳期使用氟西汀对子代大鼠行为学及5-羟色胺转运体和色氨酸羟化酶影响研究  

The effects of offspring's behavior and SERT and TPH during the lactation exposure to fluoxetine

作　　者：成熟 陈茉弦[3] 蒋玲 雷蕾[1] 周娅[1] 陈倩[1] 敖丽娟[3] 

机构地区：[1]昆明医科大学 [2]华润武钢总医院康复科,武汉430080 [3]昆明医科大学第二附属医院康复科 [4]曲靖市中心医院康复科

出　　处：《中国神经精神疾病杂志》2016年第11期641-646,共6页Chinese Journal of Nervous and Mental Diseases

基　　金：国家自然科学基金(编号:81260296);昆明医科大学第二附属医院2015年研究生创新基金(编号:2015S90)

摘　　要：目的观察哺乳期使用氟西汀对子代大鼠行为学及5一羟色胺转运体（serotonin transporter，SERT）和色氨酸羟化酶（tryptophan hydroxylase，TPH）蛋白的影响。方法妊娠SD大鼠随机分为2组，每组各3只。待分娩后5—21d予以实验组母鼠腹腔注射氟西汀（12mg/kg），对照组母鼠腹腔注射等量生理盐水，期间正常哺乳，第21d断奶。每只母鼠的子代中各挑选8只，婴儿期不同时间点分别测量体重、毛发、睁眼以评价生长发育，听觉、埋藏食物小球和自由悬挂实验评价其神经反射和运动行为；儿童期和青年期（出生后35d和75d）分别取实验组和对照组子代大鼠各6只，取脑组织行免疫组织化学染色检测前额皮质SERT及TPH水平。结果婴儿期氟西汀组子代大鼠体重较对照组低（P〈0．05），听觉敏感性得分较对照组高（P〈0．01），自由悬挂实验时间较对照组短（P〈0．01）。儿童期和青年期时氟西汀组子代前额皮质SERT及TPH均较对照组降低（P〈0．05）。结论哺乳期母鼠暴露于氟西汀可能通过下调子代大鼠前额皮质SERT和TPH导致其发育和行为异常。Objective To explore the influence of the lactation exposure to fiuoxetine on offspring＇ s behavior and serotonin transporter （SERT） and tryptophan hydroxylase （TPH）. Methods Six SD pregnant rats were randomly divided into 2 groups （n=3 each group）. Experimental maternal rats were intraperitoneally injected with fluoxetine at a dose of 12 mg/kg from postnatal day 5 to 21. The control group were injected with the same amount of normal saline. In infancy, the offspring＇ s weight, hair length, eye opening and auditory development were measured. The free suspension test and bur- ied food pellets test were applied to evaluate the offspring＇ s behaviors. After postnatal day 21, all the offspring were wean. At early childhood （P35d） and adulthood （P75d）, 6 offspring rats from each group were executed to examine SERT and TPH in the prefrontal cortex by immunohistochemistry. Results The offspring＇ s weight of experimental group was significantly lower than control group （P〈0.05）. The sensitivity of auditory in experimental group was significantly higher than control group （P〈0.01）. The time of free suspension in experimental group significantly was decreased comparing to control group （P〈0.01）. The SERT and TPH in prefrontal cortex was significantly lower in experimental group than those in control group either at childhood （P35d） or at adulthood （P75d） （P〈0.05）. Conclusion Lactation exposure to fluoxetine resuits in offspring＇ s abnormal development and behaviors through down-regulation of SERT and TPH in the prefrontal cortex.

关 键 词：哺乳期 氟西汀 行为学 5-羟色胺转运体 色氨酸羟化酶 

分 类 号：R749.94[医药卫生—神经病学与精神病学]