Pharmacotherapy Impact on Cocaine and Alcohol-derived Reinforcement.

说明（由申请人提供）：可卡因的使用、滥用和依赖是一个公共卫生问题，每年直接造成数千亿美元的卫生保健支出。可卡因使用的复发率很高，迫切需要开发有效的治疗可卡因依赖的方法。因此，这项研究对于进一步了解可卡因依赖和开发有效的新疗法非常重要。本申请的目的是为宾夕法尼亚大学成瘾研究中心（CSA）的博士后Jennifer G. Plebani博士奠定基础，使她成为一名具有可卡因依赖药物治疗专业知识的独立研究者，并专注于人类实验室研究。该提案建立在她对物质依赖人类行为实验室研究的现有知识，以及通过精心组织的培训和研究计划，包括教学培训，课程作业和经验实验室培训，在物质依赖方面的有限临床经验的基础上。在这个奖项的过程中。普莱巴尼博士将在海伦·佩蒂纳蒂博士的博士后指导下继续研究治疗可卡因依赖。她将由一组具有可卡因药物治疗（O'Brien和Kampman）、人体实验室研究（Oslin）、可卡因自我给药研究（Hart）、药物衍生强化研究（Walsh）以及受试者交叉设计的统计分析和研究设计（Lynch）经验的研究人员指导。拟议的研究和培训将侧重于调查可卡因依赖的决定因素和后果，方法是在实验室测量急性剂量可卡因对人类志愿人员的生理、行为和主观影响，并审查药物疗法对可卡因上述影响的影响。拟议的两项研究将在为期一周的亚慢性伐尼克兰（Chantix）剂量和安慰剂条件下（研究1），以及在为期一周的亚慢性石杉碱A剂量和安慰剂条件下（研究2）检查可卡因衍生的强化。每项研究均采用受试者内交叉设计。该K0I奖将使Plebani博士能够建立所需的专业知识，以确保未来人类行为药理学实验室对可卡因依赖的研究获得R0I资助。公共卫生相关性：可卡因的使用、滥用和依赖是一个公共卫生问题，每年直接造成数千亿美元的卫生保健支出。到目前为止，还没有发现治疗可卡因依赖的有效药物。该项目的目的是检查胆碱能药物治疗可卡因依赖的潜在疗效。

DESCRIPTION (provided by applicant): Cocaine use, abuse and dependence is a public health problem that is directly responsible for hundreds of billions of dollars in health care expenditures per year. Relapse rates to cocaine use are high, creating a pressing need to develop effective therapies for cocaine dependence. As such, this research is important for furthering understanding of cocaine dependence, and for developing effective new treatments. The purpose of this application is to lay the foundation for Dr. Jennifer G. Plebani, Ph.D., a Postdoctoral Fellow at the University of Pennsylvania Center for Studies of Addiction (CSA), to become an independent investigator with expertise in pharmacotherapies for cocaine dependence, and a focus on human laboratory studies. The proposal builds on her existing knowledge of human behavioral laboratory studies for substance dependence, and limited clinical experience in substance dependence through a carefully structured training and research program involving didactic training, coursework, and experiential laboratory training. During the course of this award. Dr. Plebani will build on the postdoctoral mentorship she Is currently receiving from Dr. Helen Pettinati in treating cocaine dependence. She will be mentored by a team of investigators with experience in pharmacotherapies for cocaine (O'Brien and Kampman), human laboratory studies (Oslin), cocaine self-administration studies (Hart), studies of drug-derived reinforcement (Walsh), and statistical analysis and study design for within-subjects cross-over designs (Lynch). The proposed research and training will focus on investigating the determinants and consequences of cocaine dependence via measurement of physiological, behavioral and subjective effects of acute doses of cocaine in human volunteers in the laboratory, and through examination of the effects of pharmacotherapies on the above effects of cocaine. The two studies proposed will examine cocaine-derived reinforcement under week-long sub-chronic varenicline (Chantix") dosing, and under placebo conditions (Study 1), and under week-long sub-chronic Huperzine A dosing, and under placebo conditions (Study 2). Each study is a within-subjects crossover design. This K0I award will allow Dr. Plebani to establish the expertise required to secure R0I funding for future human behavioral pharmacology laboratory studies of cocaine dependence. PUBLIC HEALTH RELEVANCE: Cocaine use, abuse and dependence represent a public health problem that Is directly responsible for hundreds of billions of dollars in health care expenditures per year. As yet, no efficacious pharmacotherapies for cocaine dependence have been found. The goal of this project is to examine the potential efficacy of cholinergic medications in treating cocaine dependence.