Developmental Interactions of methamphetamine and stress

甲基苯丙胺与压力的发育相互作用

• 批准号: 6477884
• 负责人: MICHAEL T WILLIAMS
• 金额: $ 11.28万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6477884
• 关键词: adrenocorticotropic hormone; behavioral /social science research tag; cell proliferation; cognition disorders; corticosteroid receptors; corticosterone; dendritic cells; developmental genetics; developmental neurobiology; developmental psychology; drug abuse; gene expression; hippocampus; hormone regulation /control mechanism; hypothalamic pituitary adrenal axis; laboratory rat; learning; memory; methamphetamine; microarray technology; neuroanatomy; neurotoxicology; neurotransmitters; neurotrophic factors; receptor expression; stress

DESCRIPTION: (Provided by Applicant) My immediate goals are to establish myself as an independent researcher, to gain an understanding for the interaction of methamphetamine (MA) and the hypothalamic-pituitary-adrenal (HPA) axis during development, and to increase my experience in methods related to learning and memory. For my long-term goals, I see myself in an academic position that allows for interaction among a variety of fields and interests with the possibility of collaborative work. I would like to be in a position to be promoted to a tenure track position and to gain tenure. My research pursuits will continue to be in the areas of drugs of abuse, development, learning and memory, neurotrophic factors, gene expression, and hormones. I feel that concurrent investigation of these areas will provide possible mechanisms for the development of cognitive deficits following drug exposure. Since very little research has incorporated all of these areas in a focused manner, this research will enable me to have a strong influence in developmental problems associated with early drug exposure, especially MA. MA use has reached epidemic proportions in a very short period of time. Very few data exist for the effects of MA during development in humans, therefore of particular concern is that women of childbearing age are among the growing number of users/abusers. Research in Dr. Charles V. Vorhees' laboratory, the mentor for the proposed application, has demonstrated that rats exposed to MA during a period of hippocampal development that correlates with third trimester human development, show cognitive impairments as adults, without apparent alterations to neurotransmitters or neurotoxicity during drug administration. Recently we have demonstrated that MA administration on P11-20 causes elevated corticosterone (CORT) and ACTH levels. The proposed studies will investigate the interaction of MA and the hormones of the HPA axis to determine if the elevation in these hormones mediates the cognitive deficits. Several converging lines of research will be used to determine these effects. Investigations will include assessing the dose-dependent response of the HPA axis to MA, the critical period of hormone release, the effect early MA exposure has on the development of the HPA axis and release of these hormones following exposure to an environmental challenge (either forced swim in a novel environment, or a novel environment alone). Further, experiments investigating the effect of CORT on cell proliferation, development, and receptors has been proposed. Investigation of gene expression changes will be undertaken. The use of different strains of rats prone to hyper- or hyposecretion of HPA axis hormones will be used, as will animals that are exposed to MA without the concurrent increase in CORT.

描述：(申请人提供) 我的近期目标是让自己成为一名独立的研究员， 了解甲基苯丙胺(MA)与 下丘脑-垂体-肾上腺(HPA)轴在发育过程中，并增加 我在学习和记忆相关方法方面的经验。为了我的长期生活 目标，我认为自己处于一个学术地位，允许 不同的领域和兴趣，具有协同工作的可能性。我 我希望能够被提升到终身教职轨道的职位，并 获得终身教职。我的研究方向将继续在毒品领域 滥用，发育，学习和记忆，神经营养因子，基因表达， 和荷尔蒙。我认为，同时对这些地区进行调查将提供 药物后认知障碍发生的可能机制 曝光。由于很少有研究将所有这些领域整合到一个 以专注的态度，这次研究将使我在 与早期药物暴露相关的发育问题，特别是MA。体量 在很短的时间内，使用已经达到了流行的程度。很少 有关于MA在人类发育过程中的影响的数据，因此 尤其令人担忧的是，育龄妇女是日益增长的 使用者/虐待者的数目。在Charles V.Vorhees博士的实验室进行的研究 Mentor建议的应用程序，已经证明暴露于MA的大鼠 在与晚期妊娠相关的海马体发育期间 人类发育，成年后表现出认知障碍，没有明显的 用药期间神经递质的变化或神经毒性。 最近，我们已经证明，在P11-20上使用MA会导致 皮质酮(CORT)和ACTH水平。拟议的研究将调查 MA和HPA轴激素的相互作用决定是否 这些荷尔蒙的升高调节了认知缺陷。几个汇聚 将使用一系列研究来确定这些影响。调查将会 包括评估HPA轴对MA的剂量依赖性反应， 激素释放的关键期，早期MA暴露对 暴露后HPA轴的发育和这些激素的释放 环境挑战(要么被迫在新的环境中游泳，要么 仅仅是新颖的环境)。此外，对皮质醇的影响进行了实验研究。 关于细胞增殖、发育和受体的研究已经提出。 将进行基因表达变化的调查。对.的使用 不同品系大鼠HPA轴激素分泌过多或过少 将被使用，就像在没有并发的情况下暴露于MA的动物一样 增加CORT。