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（由应用程序提供）：这是一种修订后的研究人员发射的R01应用程序，旨在了解甲基苯丙胺成瘾的基础神经生物学机制，以及旨在策划药物滥用的药物治疗的影响。具体而言，烟碱乙酰胆碱受体（NACHR）在甲基苯丙胺与滥用相关的作用中的作用知之甚少。例如，临床前和临床研究中的间接NACHR激动剂或拮抗剂报道了甲基苯丙胺与滥用相关的作用下降。这项申请提案解决了关于NACHR在甲基苯丙胺与滥用相关作用中的作用的科学进步的关键障碍。我们的工作假设是，甲基苯丙胺与滥用相关的作用是通过多巴胺（DA）和乙酰胆碱（ACH）释放介导的。根据，我们提出了使用恒河猴内部主题内设计的以下特定目标。 AIM＃1将确定DA和NACHR激动剂和拮抗剂对甲基苯丙胺的区分刺激作用的影响。 AIM＃2将确定维护对间接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。