Differential Effects of Methamphetamine and Cocaine

由于强效兴奋剂的持续滥用以及相关的不良社会和个人后果，本方案项目的总体目标是阐明甲基苯丙胺（METH）和可卡因（COC）等强效兴奋剂滥用的作用机制。特别是，在修订后的申请中，将由项目测试的流行假设是，由于METH和COC的不同神经化学机制，特别是转运蛋白和相关功能，它们的给药产生了显著不同的影响。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。犹他州大学与（a）成瘾研究和教育中心，（B）抗惊厥筛选项目和（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测试整体假设。这些项目的名称及其目标是： 耐受性诱导（项目#1）-该项目将确定由递增剂量的甲基而不是COC引起的耐受性的性质以及影响机制。二. VMAT和神经毒性（项目#2）-该项目将确定METH和CC对VMAT的相反作用如何导致神经毒性的存在或不存在。三.神经肽和神经毒性（项目#3）-该项目将研究阿片肽系统对METH和COC的不同反应对这些兴奋剂独特神经毒性特征的作用。四.癫痫发作诱导（项目#4）-该项目将确定由高剂量甲基苯丙胺和COC诱发的癫痫发作的独特特征及其潜在机制。在支持作用中，行政核心将作为该计划的主要决策，评估和行政单位;而资源核心将通过为项目提供高质量，集中的动物和技术服务来提高效率和质量，并降低费用。

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.