Developmental Interactions of methamphetamine and stress

甲基苯丙胺与压力的发育相互作用

• 批准号: 6878936
• 负责人: MICHAEL T WILLIAMS
• 金额: $ 11.67万
• 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/6878936
• 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） 我的近期目标是建立自己作为一个独立的研究人员， 了解甲基苯丙胺（MA）与 下丘脑-垂体-肾上腺（HPA）轴在发展过程中，并增加 我在学习和记忆方法方面的经验。对于我的长期 目标，我看到自己在一个学术地位，允许互动之间的一个 各种领域和兴趣与合作的可能性。我 我希望能够晋升到终身职位， 获得终身职位我的研究将继续在药物领域， 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，同时调查这些地区将提供 药物治疗后认知功能障碍的可能机制 exposure.由于很少有研究将所有这些领域纳入一个 专注的方式，这项研究将使我有很强的影响力， 与早期药物暴露相关的发育问题，尤其是MA。马 使用在很短的时间内就达到了流行病的程度。很少 存在MA在人类发育过程中影响的数据，因此 特别令人关切的是，育龄妇女是越来越多的 使用者/滥用者的数量。查尔斯·V·沃希斯博士实验室的研究， 建议应用的导师，已经证明，大鼠暴露于MA 在海马体发育期间， 人类发展，表现出认知障碍，作为成年人，没有明显的 给药期间神经递质或神经毒性的改变。 最近我们已经证明，P11-20的MA给药会导致P11-20的MA水平升高， 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，以确定是否 这些激素的升高介导了认知缺陷。几个收敛 将使用研究路线来确定这些影响。调查将 包括评估HPA轴对MA的剂量依赖性反应， 激素释放的关键时期，早期MA暴露对 HPA轴的发展和这些激素的释放， 环境挑战（在新环境中强迫游泳，或 单独的环境）。此外，研究CORT作用的实验 对细胞增殖、发育和受体的影响。 将进行基因表达变化的研究。使用 不同品系的大鼠易于HPA轴激素分泌过多或过少 与暴露于MA但未同时 CORT增加。