PERINATAL AZT: BEHAVIORAL EFFECTS IN A RAT MODEL

围产期 AZT：大鼠模型的行为影响

• 批准号: 2403641
• 负责人: DIANA L DOW-EDWARDS
• 金额: $ 21.38万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2403641
• 关键词: amphetamines; animal developmental psychology; behavioral /social science research tag; biological models; chemical stimulation; developmental neurobiology; embryo /fetus drug adverse effect; laboratory rat; neuropharmacology; newborn animals; pharmacokinetics; psychopharmacology; zidovudine

DESCRIPTION (adapted from the Abstract): This application is for support to study the effects of developmental AZT exposure in a laboratory rat model. AZT is an effective antiretroviral drug with relatively low toxicity in adults. Because the CDC has proposed recently the HIV testing for all pregnant women, the detection of HIV-positive women and the use of AZT, which has been shown to reduce substantially transmission of HIV from mother to fetus, will undoubtedly increase. The Principal Investigator and her coworkers have shown that gestational AZT administration to the rat is not overtly or structurally teratogenic but does produce neurobehavioral alterations in the offspring. In the proposed experiments, they will extend these findings by determining the critical period for the effect and the threshold dose at which the neurobehavioral alterations occur. AZT will be administered to developing rats during an exposure period which is comparable to the suggested exposure period in humans. Amphetamine will be administered to exposed offspring to determine the responsiveness of the central nervous system (CNS) to a challenge drug using measures of activity. Excitatory and inhibitory processes will be examined in the offspring by quantifying the responses to acoustic startle stimuli. Offspring will be examined during the postnatal period as well as in adulthood. Plasma drug levels at the lowest observable effect dose and the distribution of labeled AZT in the fetus/pup will also be determined.

描述（根据摘要改编）：此应用程序用于支持 研究了实验室大鼠模型中发育性AZT暴露的影响。 AZT是一种有效的抗逆转录病毒药物，毒性相对较低 成年人。 因为CDC最近提出了所有的HIV测试 孕妇，发现艾滋病毒阳性妇女和使用AZT的孕妇， 已证明可以减少母亲的艾滋病毒的大幅传播 胎儿无疑会增加。 首席调查员和她 同事表明，妊娠AZT给大鼠管理不是 公开或结构性致致神经，但确实会产生神经行为 后代的改变。 在拟议的实验中，它们将扩展 这些发现通过确定效果的关键时期和 发生神经行为改变的阈值剂量。 AZT会 在暴露期间对发育大鼠的发育 与人类建议的暴露期相比。 苯丙胺会 对暴露后代进行管理，以确定 中枢神经系统（CNS）使用活性测量来挑战药物。 兴奋性和抑制过程将在后代检查 量化对声学惊吓刺激的反应。 后代将是 在产后和成年期间检查。 血浆药物 最低观察效应剂量的水平和标记的分布 还将确定胎儿/幼犬中的AZT。