Models for the Prevention and Treatment of Drug Abuse

描述：（申请人提供）： 此K 05应用程序的总体目标是获得工资支持， 将从教学和行政职责中腾出时间， 与研究有关。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%。候选人的概况？的27 提供了药物滥用研究的一年背景，包括 出版物，演讲，引文分析，研究资金记录， 学生辅导、科学宣传和其他教育活动。一 职业目标部分描述了短期和长期计划， 在有更多时间用于研究、具体活动时实施 （包括合作），以维持杰出的研究计划 业绩，过去和未来的目标是如何混合的， 继续成功的贡献，并计划获得和提供 关于负责任的科学行为的指示。研究计划包括 由NIDA资助超过20年的2个R 01项目 并开始第三个项目，一个新的R 01正在审查中。第一准予 是一种非人类灵长类动物模型，用于研究影响 药物滥用（例如，性别、激素状态、暴露持续时间）和行为 以及减少药物滥用的药物治疗。行为经济学 使治疗效果最大化的分析将是 提出的实验。这一系列实验的总体假设是 性别和接触毒品时间等脆弱性因素 自我施用将预测更大的强化功效。相对于 治疗效果，假设女性将表现出更大的 药物自我给药的抑制作用高于男性。第二笔赠款将是 在大鼠中进行，涉及药物的遗传和其他生物决定因素， 诸如其他过度行为的滥用（例如，运动和消费 非药物物质）、性别和激素状态。这些因素将被比较 在成瘾的关键过渡阶段;获得和恢复 在药物获取被终止后寻求药物。本研究立足 假设一个倾向（个体差异）过度 针对新刺激的行为增加了对药物滥用的脆弱性， 而对药物滥用表现出更大脆弱性的老鼠， 易受治疗影响。第三项研究也将在大鼠中进行， 侧重于药物滥用加剧的潜在因素。总体假设 如果让老鼠有机会做出过度行为 针对非药物物质（例如蔗糖）或事件（例如，轮 他们会表现出对药物寻求行为的交叉敏感性， 通过获取、升级、调节/失调和 复职会有跨物种，性别，几种药物的比较 滥用，给药途径和成瘾过程的阶段。的 结果应允许识别生物学、行为学和 导致识别处于风险中的个人的环境因素 药物滥用，这些模型使用的实验干预措施将 为人类提供预防和治疗策略。

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.