Amphetamine & Brain Development: Third Trimester Model

描述（由申请人提供）： 这个建议的主要目的是测试的假设，安非他明暴露在第三个三个月相当于将导致行为障碍相关的海马功能和神经解剖学改变，在海马结构使用大鼠模型系统。育龄妇女使用安非他明和安非他明类药物是一个特别令人关切的问题。由于多种药物使用和环境因素等各种混杂变量，记录怀孕期间使用苯丙胺的有害后果的文献很少。从早期的动物研究中，安非他明已被证明是一种行为致畸剂，最近，有限数量的报告表明，产前安非他明暴露将导致神经解剖结构的变化，如前额叶皮层。在本提案中，将使用妊娠晚期模型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（特定目的#1），并使用大鼠模型系统建立行为损伤与海马结构神经解剖学改变之间的相关性（特定目的#2）。在大鼠中，大脑的快速生长期（相当于人类的第三个三个月）发生在出生后的早期，并且已经表明，这种大脑的快速生长特别容易受到神经毒剂的影响。这项建议的发现将使我们更好地了解在大脑发育的最关键时期安非他明暴露对认知功能及其与介导这些行为的大脑结构的相关性。

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.