Animal Models for the Prevention and Treatment of Drug Abuse

描述（由申请人提供）：此K05申请的目的是获得与研究不直接相关的教学和行政职责空闲时间的工资支持。这将把分配给研究的时间从K05之前的40%增加到75% - 90%。候选人在药物滥用研究方面31年的背景概述，包括出版物、演讲、引文分析、研究经费、学生指导、科学倡导和教育活动。讨论了将在公布时间内实施的短期和长期研究计划。还讨论了为维持杰出的研究表现而计划的具体活动，过去和未来目标的融合，持续成功贡献的可能性，以及在负责任的科学行为方面获得和提供指导的计划。一份进度报告描述了2002-2006年K05奖头四年所取得的成就。该研究计划包括2个持续的R01项目，已由NIDA资助超过20年，一个新的R01 （PI）正在审查中，以及一个P20申请（Co-Pi）正在审查中。第一笔拨款是一个非人类灵长类动物模型，用于研究性别、月经周期阶段和冲动作为影响药物滥用脆弱性的因素，并实施创新的药物滥用行为和药物治疗。总体假设是，这些脆弱性因素将预测强化疗效和治疗成功。第二笔拨款将用于研究针对几种易感行为选择的大鼠的行为和药物干预。这些因素将在成瘾、获取、升级和恢复的关键过渡阶段进行比较。其假设是，过度行为的倾向（个体差异）指向新颖和有益的非药物活动，增加了对药物滥用的脆弱性和对治疗的反应。第三项拨款计划将在青春期大鼠中进行，重点研究药物滥用的潜在因素。总的假设是，青春期的动物比成年动物更冲动，更容易受到荷尔蒙对药物寻求行为的影响。第四项提议的拨款是P20，将包括一个动物项目，该项目将与两个涉及可卡因滥用者和冲动行为不同的大学生的人类项目并行并提供信息。基本主题是冲动与药物滥用之间的关系，磁共振成像将在大鼠和猴子身上使用，以比较神经生物学和行为表型。将比较物种、性别、几种滥用药物、给药途径和成瘾阶段。结果将允许识别生物、行为和环境因素，从而识别有药物滥用风险的个体，并且与这些模型一起使用的实验性干预措施将为人类的预防和治疗策略提供信息。

DESCRIPTION (provided by applicant): The objective of this K05 application is to obtain salary support for release time from teaching and administrative duties not directly related to research. This would increase time allocated to research from 40% before the K05 to 75-90. An overview of the candidate's 31-year background in drug abuse research is provided including a list of publications, presentations, a citation analysis, research funding, and mentorship of students, science advocacy, and educational activities. Short-and-long-term research plans that will be implemented with released time are discussed. Specific activities planned to sustain outstanding research performance, blending of past and future goals, the likelihood of continuing successful contributions, and plans to obtain and provide instruction on the responsible conduct of science are also discussed. A progress report describes accomplishments made in the first 4 years of this K05 award 2002-2006. The research plan consists of 2 continuing R01 projects that have been funded by NIDA for over 20 years, a new R01 (PI) that is under review, and a P20 application (Co-Pi) that is under review. The first grant is a nonhuman primate model to study sex, phase of menstrual cycle, and impulsivity as factors that affect the Vulnerability to drug abuse and to implement innovative behavioral and pharmacological treatments for drug abuse. The overall hypothesis is that these vulnerability factors will predict reinforcing efficacy and treatment success. The second grant will examine behavioral and pharmacological interventions in rats selected for several vulnerable behaviors. These factors will be compared during critical transition phases of addiction, acquisition, escalation, and reinstatement. The hypothesis is that a predisposition (individual differences) for excessive behavior directed toward novel and rewarding nondrug activities increases vulnerability to drug abuse and responsiveness to treatment. The third proposed grant, to be conducted in adolescent rats, is focused on factors underlying drug abuse. The overall hypothesis is that adolescent animals are more impulsive and susceptible to hormonal influences on drug seeking behavior than adults. The fourth proposed grant, a P20, would consist of an animal project that will parallel and inform two human projects involving cocaine abusers and college students varying in impulsive behavior. The basic theme is how, impulsivity is related to drug abuse, and MR imaging will be used in rats and monkeys to compare neurobiological and behavioral phenotypes. Species, gender, several drugs of abuse, routes of administration, and phases of addiction will be compared. The results will allow for identification of biological, behavioral, and environmental factors leading to recognition of individuals at risk for drug abuse, and the experimental interventions used with these models will inform prevention and treatment strategies for humans.