Drug Abuse Methodology: Training and Interdisciplinary Application

药物滥用方法：培训和跨学科应用

• 批准号: 8242430
• 负责人: Rajeev Indrajit Desai
• 金额: $ 17.23万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8242430
• 关键词: Address; Agonist; Area; Attenuated; Award; Behavior; Behavioral; Brain; Catheters; Cocaine; Complex; Corpus striatum structure; Coupled; Decision Making; Dependence; Development; Dopamine; Drug Addiction; Drug abuse; Familiarity; Funding Mechanisms; Goals; Hospitals; Human; Image; Implant; Individual; Intravenous; Knowledge; Laboratories; Lead; Learning; Ligands; Measures; Mentored Research Scientist Development Award; Mentors; Mentorship; Methamphetamine; Methodology; Microdialysis; Nicotine; Nicotinic Agonists; Operative Surgical Procedures; Performance; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Plague; Procedures; Property; Psychostimulant dependence; Public Health; Qualifying; Reinforcement Schedule; Research; Research Methodology; Research Personnel; Research Training; Saimiri; Schedule; Scientist; Scourge; Self Administration; Self-Administered; Series; Supervision; Techniques; Time; Training; Work; addiction; base; behavioral pharmacology; career; combat; cytisine; design; epibatidine; experience; extracellular; in vivo; investigator training; medical schools; neurochemistry; nonhuman primate; novel; pre-clinical; programs; research study; skills; tool; varenicline

DESCRIPTION (provided by applicant): This K01 application responds to PA-10-056, and is intended to obtain support and "protected time" for Dr. Rajeev I. Desai (PI) to gain extensive supervised research training and experience in all aspects of intravenous (IV) self-administration methodology in non-human primates (NHP). The project is designed to systematically allow the PI to acquire necessary skills and experience to independently and expertly study the reinforcing effects of stimulant and other addictive drugs, and to couple this methodology with concurrent in vivo microdialysis to measure related neurochemical activity. The support provided by the K01 award will ultimately allow the PI to: a) develop a comprehensive program of highly translational neurochemical and behavioral studies to directly address the public health concern of stimulant addiction and the development of medications for its treatment; and b) acquire the tools necessary to independently continue and expand this line of research through R01 funding mechanisms. The aims of this project are designed to optimize the PI's training experience through a systematic series of experiments evaluating IV cocaine and nicotine self- administration behavior under simple and complex schedules of reinforcement. The PI next will couple his existing expertise with in vivo microdialysis techniques to his newly acquired behavioral skills to measure changes in striatal dopamine levels produced by cocaine and nicotine during IV self-administration performance under different schedule conditions. Finally, studies will be conducted to determine whether nicotinic agonist-based candidate medications attenuate reinforcing and neurochemical effects of self- administered nicotine or cocaine. The proposed research in this project will establish the PI as a well-trained and independent young scientist who is qualified to conduct highly translational addiction research in NHP. In addition, the planned studies may lead to the further development of promising novel nicotinic-based pharmacotherapy to help combat the scourge of stimulant addiction that plagues our public health. PUBLIC HEALTH RELEVANCE: Translational behavioral and neurochemical methodologies are an integral part of drug addiction research methodology, and there is a clear need for trained scientists who are qualified to conduct this type of multi- dimensional work in nonhuman primates. This project is designed to systematically provide a young investigator with intensive supervised research training to directly measure the reinforcing effects of addictive drugs and their associated neurochemical changes in highly translational procedures. The proposed research will lead to a greater understanding of neurochemical mechanisms in psychomotor stimulant addiction, and may identify novel nicotinic targets to help combat this public health concern.

描述（由申请人提供）：此 K01 申请响应 PA-10-056，旨在为 Rajeev I. Desai 博士（PI）获得支持和“受保护的时间”，以获得广泛的监督研究培训和各方面的经验非人类灵长类动物（NHP）静脉（IV）自我给药方法的研究。该项目旨在系统地让 PI 获得必要的技能和经验，以独立、专业地研究兴奋剂和其他成瘾药物的增强作用，并将这种方法与同时进行的体内微透析结合起来，以测量相关的神经化学活性。 K01 奖提供的支持最终将使 PI 能够： a) 开发一个高度转化的神经化学和行为研究的综合计划，以直接解决兴奋剂成瘾的公共健康问题，并开发治疗其的药物； b) 通过 R01 资助机制获得独立继续和扩展这一研究领域所需的工具。该项目的目的是通过一系列系统实验来优化 PI 的培训体验，该实验评估简单和复杂的强化计划下静脉注射可卡因和尼古丁的自我管理行为。接下来，PI 将把他现有的专业知识与体内微透析技术结合起来 根据他新获得的行为技能，测量在不同时间安排条件下静脉注射自我给药期间可卡因和尼古丁产生的纹状体多巴胺水平的变化。最后，将进行研究以确定基于烟碱激动剂的候选药物是否减弱自我施用尼古丁或可卡因的增强作用和神经化学作用。该项目拟议的研究将使 PI 成为一名训练有素、独立的年轻科学家，有资格在 NHP 中进行高度转化的成瘾研究。此外，计划中的研究可能会进一步开发有前景的新型烟碱类药物疗法，以帮助对抗困扰我们公众健康的兴奋剂成瘾祸害。 公共健康相关性：转化行为和神经化学方法是药物成瘾研究方法的一个组成部分，显然需要有资格在非人类灵长类动物中进行此类多维工作的训练有素的科学家。该项目旨在系统地为年轻研究者提供密集的监督研究培训，以直接测量成瘾药物的强化作用及其在高度转化过程中相关的神经化学变化。拟议的研究将有助于更好地了解精神运动兴奋剂成瘾的神经化学机制，并可能确定新的烟碱靶点以帮助应对这一公共卫生问题。