Functional Monoamine Deficits Induced by Amphetamines

安非他明引起的功能性单胺缺乏

• 批准号: 6810113
• 负责人: CARRIE E. JOHN
• 金额: $ 3.89万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-18 至 2006-04-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6810113
• 关键词: 3,4 methylenedioxyamphetamine; brain imaging /visualization /scanning; dopamine; dopamine transporter; drug abuse; electrophysiology; fenfluramine; genetically modified animals; laboratory mouse; methamphetamine; neurotoxicology; phentermine; predoctoral investigator; sectioning; serotonin; serotonin transporter; substantia nigra

DESCRIPTION (provided by applicant): This application proposes to assess the acute and chronic effects of methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) on dopamine (DA) and serotonin (5-HT) terminal function and evaluate the relationship between DA and 5-HT neurotoxicity. We will first compare the effects of METH and MDMA on monoamine terminal function acutely in mouse brain slices. Then we will evaluate terminal function recovery following a repeated administration paradigm. Voltammetry at carbon fiber electrodes will be used to measure release and uptake of DA and 5-HT in brain slices. With the use of the DA and the 5-HT transporter knockout mouse lines, and the selective neurotoxins phentermine and fenfluramine, we will evaluate whether DA influences 5-HT neurotoxicity, and vice versa. The research proposed will provide valuable insights into the differential long-term impact of amphetamine derivatives on monoamine systems and the potential interactions between DA and 5-HT in inducing neurotoxicity.

描述（由申请人提供）： 本申请旨在评估甲基苯丙胺（METH）和3，4-亚甲二氧基甲基苯丙胺（MDMA）对多巴胺（DA）和5-羟色胺（5-HT）末端功能的急性和慢性影响，并评价DA和5-HT神经毒性之间的关系。我们将首先比较METH和MDMA对小鼠脑片单胺末端功能的影响。然后，我们将在重复给药范例后评价终末功能恢复。在碳纤维电极上的伏安法将用于测量脑切片中DA和5-HT的释放和摄取。通过使用DA和5-HT转运蛋白敲除小鼠系以及选择性神经毒素芬特明和芬氟拉明，我们将评估DA是否影响5-HT神经毒性，反之亦然。该研究将为苯丙胺衍生物对单胺系统的长期影响以及DA和5-HT在诱导神经毒性方面的潜在相互作用提供有价值的见解。