'Differential Effects of Methamphetamine and Cocaine

由于强效兴奋剂的持续滥用及其相关的不良社会和个人后果，本项目的总体目标是阐明强效兴奋剂滥用的机制，如甲基苯丙胺（冰毒）和可卡因（COC）。特别是，在本修订申请中，项目需要测试的主流假设是，甲基苯丙胺和COC的给药由于其不同的神经化学机制，特别是对转运体和相关功能的影响，会产生显著不同的影响。我们认为，通过阐明(a)这两种药物的独特特征，(b)它们的潜在机制，以及(c)它们的独特性质和其他兴奋剂的影响。犹他大学与(a)成瘾研究和教育中心、(b)抗惊厥药物筛选项目和(c)人类毒理学中心相关的独特专业知识，使我们能够确定四个主要项目，这些项目将以高度综合的方式检验整个假设。项目名称及其目标是：1 .诱导耐受性（项目#1）-该项目将确定甲基苯丙胺（但不包括COC）剂量增加引起的耐受性的性质，以及影响机制。2。VMAT和神经毒性（项目#2）-该项目将确定甲基安非他明和CC对VMAT的相反作用如何导致神经毒性的存在或不存在。3。神经肽和神经毒性（项目#3）-该项目将研究阿片肽系统对甲基安非他明和COC的不同反应对这些兴奋剂独特的神经毒性特征的作用。iv.癫痫诱导（项目#4）-该项目将确定高剂量甲基苯丙胺和COC诱发癫痫发作的独特特征及其潜在机制。作为支持，行政核心将作为该项目的主要决策、评估和管理单位；而资源中心将通过为项目提供高质量、集中的动物和技术服务，提高效率和质量，降低费用。

Due to the persistent abuse of potent stimulants and the related adverse social and individual consequences, the overall objective of this Program Project is to elucidate the mechanisms responsible for the effects of potent stimulants of abuse, such as methamphetamine (METH) and cocaine (COC). In particular, the prevailing hypothesis to be tested by projects in this revised application is that METH and COC administration exert significantly different effects due to their distinct neurochemical mechanisms particularly to transporters and associated functions. We believe that by elucidating (a) the unique features of these two drugs, (b) their underlying mechanisms, and (c) the impact of their distinct properties, and other stimulants. The distinctive expertise at the University of Utah associated with the (a) Addiction Research and Education Center, (b) Anticonvulsant Screening Project, and (c) Center for Human Toxicology, enables to identify four principal projects that will test the overall hypothesis in a highly integrative fashion. The titles of the projects and their objectives are: i. Tolerance Induction (Project #1)-This project will determine the nature of the tolerance caused by escalating doses of METH, but not COC, and the effecting mechanism. ii. VMAT and Neurotoxicity (Project #2)-This project will determine how the opposite effects of METH and CC on VMAT contributes to the presence or absence of neurotoxicity. iii. Neuropeptides and Neurotoxicity (Project #3)-This project will examine the role of differential response by opioid peptide systems to METH and COC on the unique neurotoxic features of these stimulants. iv. Seizure Induction (Project #4)-This project will determine the unique features of seizures evoked by high doses of METH and COC and the underlying mechanisms. In a supportive role, the Administrative Core will function as the principal decision-making, evaluative, and administrative unit for this program; while the Resource Core will enhance efficiency and quality, and reduce expenses by providing high-quality, centralized animal and technology services for the project.