Long-term effects of developmental exposure to zidovudine on exploratory behavior and novelty discrimination in CD-1 mice
Long-term effects of developmental exposure to zidovudine on exploratory behavior and novelty discrimination in CD-1 mice
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DOI：
10.1016/s0892-0362(02)00234-9
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发表时间：
2002-07-01
影响因子：
2.9
通讯作者：
Puopolo, M
中科院分区：
文献类型：
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作者：
Calamandrei, G;Rufini, O;Puopolo, M
据报道，在发育过程中接触齐多夫定(AZT)后，啮齿动物的探索性、社会性和激励性行为发生了长期变化。齐多夫定是一种通常用于孕妇血清阳性妇女及其新生儿以防止HIV-1传播的药物。本研究通过四个物体的开场测试，评估了产前或延长AZT治疗对小鼠空间和非空间新颖性辨别的影响，其中包括对熟悉物体的空间重排和物体新颖性的反应。AZT(160 mg/kg)或生理盐水分别于妊娠第10天至19日(实验1)或妊娠第10天至哺乳期第10天(实验2)灌胃，每日2次。在出生后28天、45天或70天对雌雄交配的后代进行检测。根据治疗方案的不同，AZT改变了不同的行为反应，男性比女性受到的影响更大。产前治疗(实验1)减少了所有年龄段对对象的探索，并在45岁和70岁时增加了墙面和顶部的养育。延长治疗后(实验2)，AZT后代明显比对照组更活跃，在70岁时表现出更多的墙体养育，而在所有年龄段都表现出较低的梳理频率。AZT和对照组小鼠在成年时都没有对物体重排做出反应，这与之前的数据不同，这一数据与围产期应激效应有关。(C)2002 Elsevier Science Inc.保留所有权利。
Long-term changes in exploratory, social and agonistic behavior have been reported in rodents following developmental exposure to zidovudine (AZT), an agent commonly administered to pregnant seropositive women and their neonates to prevent HIV-1 transmission. The present study evaluates the effects of either prenatal or prolonged AZT treatment on spatial and nonspatial novelty discrimination in mice, using an open-field test with four objects, in which responses to both spatial rearrangement of familiar objects and object novelty are assessed. AZT (160 mg/kg) or Saline was given orally twice daily to pregnant mice from gestational days (GD) 10 to 19 (Experiment 1) or from GD 10 to lactation day 10 (Experiment 2). Offspring of both sexes were tested on postnatal day (PND) 28, 45 or 70. Depending on treatment schedule, AZT altered different behavioral responses, males being more affected than females. The prenatal treatment (Experiment 1) reduced exploration of the objects at all ages considered and increased wall and top rearing at ages 45 and 70. Following prolonged treatment (Experiment 2), AZT offspring were markedly more active than controls and displayed more wall rearing at age 70 while showing lower grooming frequency at all ages. Both AZT and control mice failed to respond to object rearrangement at adulthood, a discrepancy from previous data, which is discussed in relation to perinatal stress effects. (C) 2002 Elsevier Science Inc. All rights reserved.