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Treatment Development for Methamphetamine Abuse

甲基苯丙胺滥用的治疗方法开发

基本信息

批准号：
8693993
负责人：
Matthew L Banks
金额：
$ 39.67万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-15 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8693993
关键词：
Acetylcholine Address Agonist Attenuated Bupropion Clinical Clinical Research Development Dopamine Dopamine Agonists Dopamine Antagonists Dopamine Receptor Dose Drug Addiction Drug usage Experimental Designs Goals Knowledge Macaca mulatta Maintenance Mecamylamine Mediating Methamphetamine Methamphetamine dependence Modafinil Nicotinic Receptors Outcome Patients Pharmaceutical Preparations Pharmacological Treatment Pharmacotherapy Process Pseudoephedrine Public Health Reporting Research Research Personnel Residual state Risk Role Self-Administered Stimulus Substance abuse problem System Testing Translations United States Food and Drug Administration Work base design dopamine system dopamine transporter effective therapy experimental analysis extracellular inhibitor/antagonist innovation methamphetamine abuse monoamine neurobiological mechanism pre-clinical preclinical study response stimulant abuse therapy development treatment strategy

项目摘要

DESCRIPTION (provided by applicant): This is a revised New Investigator-initiated R01 application designed to understand the neurobiological mechanisms underlying methamphetamine addiction, as well as the effects of pharmacological treatments aimed at curbing substance abuse. Specifically, the role of nicotinic acetylcholine receptors (nAChRs) in the abuse-related effects of methamphetamine is poorly understood. For example, indirect nAChR agonists, or antagonists in preclinical and clinical studies have reported decreases in the abuse-related effects of methamphetamine. This application proposes to address this critical barrier to scientific progress regarding the role of nAChR in the abuse-related effects of methamphetamine. Our working hypothesis is that the abuse-related effects of methamphetamine are mediated through combined dopamine (DA) and acetylcholine (ACh) release. Accordingly, we propose the following Specific Aims using a within-subjects design in rhesus monkeys. Aim#1 will determine the effects of DA and nAChR agonists and antagonists on the discriminative stimulus effects of methamphetamine. Aim#2 will determine the effects of maintenance on an indirect DA agonist or DA antagonist ¿ nAChR antagonist on the reinforcing effects of methamphetamine.

描述（由申请人提供）：这是一项修订后的新研究者发起的R01申请，旨在了解甲基苯丙胺成瘾的神经生物学机制，以及旨在遏制药物滥用的药理学治疗的效果。具体而言，烟碱乙酰胆碱受体（nAChRs）在甲基苯丙胺滥用相关效应中的作用知之甚少。例如，临床前和临床研究中的间接nAChR激动剂或拮抗剂报告了甲基苯丙胺滥用相关作用的减少。该申请旨在解决nAChR在甲基苯丙胺滥用相关影响中的作用这一科学进步的关键障碍。我们的工作假设是，滥用相关的影响，甲基苯丙胺介导的多巴胺（DA）和乙酰胆碱（ACh）的联合释放。因此，我们在恒河猴中使用受试者内设计提出了以下特定目的。目标#1将确定DA和nAChR激动剂和拮抗剂对甲基苯丙胺的辨别刺激作用的影响。目标2将确定维持间接DA激动剂或DA拮抗剂nAChR拮抗剂对甲基苯丙胺增强作用的影响。