Pharmacotherapy Impact on Cocaine and Alcohol-derived Reinforcement.

描述(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，每年直接导致数千亿美元的医疗保健支出。使用可卡因的复发率很高，迫切需要开发有效的可卡因依赖疗法。因此，这项研究对于加深对可卡因依赖的理解和开发有效的新疗法具有重要意义。这份申请的目的是为宾夕法尼亚大学成瘾研究中心(CSA)博士后Jennifer G.Plebani博士成为一名独立调查员奠定基础，她在可卡因依赖的药物疗法方面拥有专业知识，并专注于人体实验室研究。这项建议建立在她对物质依赖的人类行为实验室研究的现有知识和有限的物质依赖临床经验的基础上，通过精心构建的培训和研究计划，包括说教培训、课程作业和体验式实验室培训。在这个奖项的过程中。普莱巴尼博士将在她目前从海伦·佩蒂纳蒂博士那里获得的治疗可卡因依赖的博士后导师的基础上再接再厉。她将得到一个研究团队的指导，他们在可卡因的药物疗法(O‘Brien和Kampman)、人体实验室研究(奥斯林)、可卡因自我给药研究(HART)、药物衍生强化研究(Walsh)以及受试者内交叉设计的统计分析和研究设计(Lynch)方面都有经验。拟议的研究和培训将侧重于通过在实验室测量急性剂量可卡因对人类志愿者的生理、行为和主观影响，以及通过检查药物疗法对可卡因上述影响的影响，来调查可卡因依赖的决定因素和后果。建议的两项研究将在亚慢性伐伦克林(Chantix)一周剂量和安慰剂条件下(研究1)和在亚慢性石杉碱甲一周剂量下和在安慰剂条件下(研究2)检查可卡因衍生强化。每项研究均为受试者内交叉设计。这项K0I奖将允许Plebani博士建立所需的专业知识，为未来可卡因依赖的人类行为药理学实验室研究获得R0I资金。与公共卫生相关：可卡因的使用、滥用和依赖是一个公共卫生问题，直接导致每年数千亿美元的医疗保健支出。到目前为止，还没有找到治疗可卡因依赖的有效药物疗法。该项目的目标是检查胆碱能药物在治疗可卡因依赖方面的潜在疗效。

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.