Amphetamine & Brain Development: Third Trimester Model

安非他明

• 批准号: 6964620
• 负责人: ANDREW M SMITH
• 金额: $ 2.89万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-11-02 至 2007-11-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6964620
• 关键词: amphetamines; behavior test; cognition disorders; dentate gyrus; developmental neurobiology; embryo /fetus toxicology; hippocampus; laboratory rat; mossy fiber; neural degeneration; neurogenesis; predoctoral investigator; pregnancy

DESCRIPTION (provided by applicant): The primary intention of this proposal is to test the hypothesis that amphetamine exposure during the third trimester equivalent will lead to behavioral impairments related to hippocampal function and neuroanatomical alterations in the hippocampal formation using a rat model system. The use of amphetamine, and amphetamine-like drugs, by women of reproductive age is an issue of particular concern. There is a scarcity of literature documenting the detrimental consequences of amphetamine use during pregnancy due to various confounding variables, such as polydrug use and environmental factors. From earlier animal studies, amphetamine has been shown to be a behavioral teratogen and more recently, a limited number of reports indicate that prenatal amphetamine exposure will result in changes in neuroanatomical structures, such as the prefrontal cortex. In this proposal, a third trimester model will be used to investigate the effects of developmental amphetamine exposure on two learning and memory tasks that are linked to the functions of the hippocampal formation (SPECIFIC AIM #1), and to establish the correlations between behavioral; impairments with neuroanatomical alterations in the hippocampal formation (SPECIFIC AIM #2) using a rat model system. In rats, the period of rapid brain growth (equivalent to the third trimester in humans) occurs during early postnatal life, and it has been shown that this brain growth spurt is particularly vulnerable to neurotoxic agents. The findings of this proposal will allow a better understanding of amphetamine exposure during the most critical period of bra n development on cognitive functions and their correlations with the brain structures mediating these behaviors.

描述（由申请人提供）： 该提案的主要目的是使用大鼠模型系统检验以下假设：妊娠晚期期间接触安非他明会导致与海马功能相关的行为障碍和海马结构的神经解剖学改变。育龄妇女使用苯丙胺和苯丙胺类药物是一个特别值得关注的问题。由于多种混杂变量，例如多种药物的使用和环境因素，很少有文献记录怀孕期间使用安非他明的有害后果。早期的动物研究表明，安非他明是一种行为致畸剂，最近，有限的报告表明，产前接触安非他明会导致神经解剖结构（例如前额皮质）的变化。在本提案中，将使用妊娠晚期模型来研究发育性安非他明暴露对与海马结构功能相关的两项学习和记忆任务的影响（具体目标#1），并建立行为之间的相关性；使用大鼠模型系统研究海马结构神经解剖学改变造成的损伤（具体目标#2）。在大鼠中，大脑快速生长期（相当于人类的妊娠晚期）发生在产后早期，并且研究表明，这种大脑生长突增期特别容易受到神经毒剂的影响。该提案的研究结果将有助于更好地了解在大脑发育最关键时期接触安非他明对认知功能的影响及其与介导这些行为的大脑结构的相关性。