Models for the Prevention and Treatment of Drug Abuse

描述：(申请人提供)： 此K05应用程序的总体目标是获得以下薪资支持 将把时间从非直接的教学和行政职责中解放出来 与研究相关。这将有效地增加分配给研究的时间 从目前的40%提高到75%-90%。候选人概述？S 27岁 提供了药物滥用研究的年份背景，包括 出版物、演示文稿、引文分析、研究经费记录、 学生辅导、科学倡导和其他教育活动。一个 职业目标部分描述了短期和长期计划，将 当腾出更多时间用于研究、特定活动时实施 (包括合作)计划支持杰出的研究 绩效、过去和未来目标的融合方式、 继续成功捐款，并计划获得和提供 关于负责任的科学行为的指导。研究计划包括 在NIDA资助了20多年的持续2个R01项目中 并开始第三个项目，新的R01正在审查中。第一笔赠款 是一种非人类灵长类动物模型，用于研究影响易感性的因素 药物滥用(例如，性别、荷尔蒙状况、吸毒持续时间)和行为 以及减少药物滥用的药物治疗。行为经济学 最大限度地发挥治疗效果的分析将是 拟议的实验。这一系列实验的总体假设是 性别和吸毒时间等易感因素 自我管理将预示着更大的强化效果。关于…… 治疗效果，假设女性会表现出更大的 对药物自我给药的抑制作用高于男性。第二笔赠款将是 在大鼠身上进行，涉及药物的遗传和其他生物决定因素 滥用，如其他过度行为(例如，锻炼和消费 非药物物质)、性别和荷尔蒙状况。这些因素将被比较 在成瘾、习得和恢复的关键过渡阶段 在毒品接触被终止后寻求毒品的情况。这项研究是基于 基于这样一种假设，即过度的倾向(个体差异) 针对新刺激的行为会增加药物滥用的易感性， 而对药物滥用表现出更大脆弱性的老鼠将会有更多 易受治疗的。第三项资助也将在大鼠身上进行， 重点关注药物滥用升级的潜在因素。总体假设 如果让老鼠有机会做出过度的行为 指向非药物物质(例如蔗糖)或事件(例如车轮 跑步)，他们会表现出对寻求毒品行为的交叉敏感化 通过收购、升级、监管/失调和 复职。将进行跨物种、性别和几种药物的比较 滥用、给药途径和成瘾过程的阶段。这个 结果应允许识别生物学、行为学和 导致认识到处于危险中的个人的环境因素 对于药物滥用，使用这些模型的实验干预将 告知人类的预防和治疗策略。

DESCRIPTION: (Provided by Applicant): The overall objective of this K05 application is to obtain salary support that will release time from teaching and administrative duties that are not directly related to research. This would effectively increase time allocated to research from the current 40 percent to 75-90 percent. An overview of the candidate?s 27 year background in drug abuse research is provided including a list of publications, presentations, a citation analysis, a record of research funding, mentorship of students, science advocacy and other educational activities. A section on career goals describes short- and long-term plans that will be implemented when more time is released for research, specific activities (including collaborations) that are planned to sustain outstanding research performance, how past and future goals are blended, the likelihood of continuing successful contributions, and plans to obtain and provide instruction on the responsible conduct of science. The research plan consists of continuing 2 R01 projects that have been funded by NIDA for over 20 years and beginning a third project, a new R01 that is under review. The first grant is a nonhuman primate model to study factors that affect the vulnerability to drug abuse (e.g., sex, hormonal status, duration of expsoure) and behavioral and pharmacological treatments that reduce drug abuse. Behavioral economic analyses that maximize treatment effects will be a procedural focus at the proposed experiments. The overall hypothesis for this series of experiments is that vulnerability factors such as sex and duration of exposure to drug self-administration will predict greater reinforcing efficacy. With respect to treatment effects, it is hypothesized that females will show a greater suppression of drug self-administration than males. The second grant to be conducted in rats, concerns genetic and other biological determinants of drug abuse such as other excessive behaviors (e.g., exercise and consumption of nondrug substances), sex, and hormonal status. These factors will be compared during critical transition phases of addiction; acquisition and reinstatement of drug seeking after drug access has been terminated. This research is based on the hypothesis that a predisposition (individual differences) for excessive behavior directed toward novel stimuli increases vulnerability to drug abuse, and that rats showing greater vulnerability to drug abuse will be more susceptible to treatment. The third grant, also to be conducted in rats, is focused on factors underlying escalation of drug abuse. The overall hypothesis is that if rats are given the opportunity to engage in excessive behavior directed toward nondrug substances (e.g. sucrose) or events (e.g., wheel running), they will show cross-sensitization to drug seeking behavior as measured by models of acquisition, escalation, regulation/dysregulation and reinstatement. There will be comparisons across species, gender, several drugs of abuse, routes of administration, and phases of the addiction process. The results should allow for identification of biological, behavioral and environmental factors that lead to recognition of individuals who are at risk for drug abuse, and the experimental interventions used with these models will inform prevention and treatment strategies for humans.