CRAVING AND SENSITIZATION MODELS IN INBRED MICE STRAINS

近交小鼠品系的渴望和致敏模型

• 批准号: 2842161
• 负责人: STEPHEN Cletius FOWLER
• 金额: $ 12.47万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2842161
• 关键词: amphetamines; behavioral /social science research tag; behavioral habituation /sensitization; cocaine; conditioning; craving; disease /disorder model; ethanol; genetic strain; genetic susceptibility; laboratory mouse; model design /development; naltrexone; reinforcer; substance abuse related behavior

DESCRIPTION: (Adapted From The Applicant's Abstract): The proposed research aims to develop a behavioral laboratory model of drug craving in the mouse and to identify individual differences in craving behavior produced by differences in genetic endowment. The first specific goal is to examine a reward-seeking/self- administration paradigm with two inbred strains (Balb/c and C57Bl/6) and one outbred (CD-1) strain of mice. These initial studies will identify optimal parameters for measuring craving- related behaviors in addressing the second and fourth goals. Our second goal is to test the drug-seeking/ oral self-administration procedure using ethanol reward, the ethanol-consuming C57Bl/6 mice, and the anti-craving medication naltrexone. The third goal, to be accomplished in a new type of force plate movement analyzer, is to characterize sensitization and conditioned drugs effects of cocaine and amphetamine in the same three strains of mice. According to contemporary theories of drug abuse, sensitization and conditioned drug effects are key factors in craving and relapse, and our preliminary data with the force plate sensor suggest that conditioned drug effects and sensitization are measurable in terms of both spatial and temporal patterns of behavior. A fourth major goal is to develop a hybrid apparatus that incorporates both the operant methods and the force plate sensor so that reward-seeking behavior can be studied with both methods concurrently. In accomplishing the fourth goal all three strains of mice will be used. Throughout these studies, we will apply state-of-the-art computer recording techniques to the measurement of the physical characteristics of the instrumental response involved in reward- seeking and self-administration and quantify strain-specific sensitization and conditioned drug responses. Developing an animal model, such as this, will provide some of the basic information needed to understand how environmental context, individual differences in genetic endowment, and pharmacological variables influence drug craving, drug seeking and ultimately drug taking. In addition, future work with these methods should result in more effective pre-clinical evaluation of potentially effective treatment and prevention strategies of drug craving for a variety of abused drugs.

描述：（改编自申请人摘要）：本研究旨在建立小鼠药物渴求的行为实验室模型，并确定基因天赋差异导致的渴求行为的个体差异。第一个具体目标是研究两种近交系（Balb/c和C57Bl/6）和一种远交系（CD-1）小鼠的奖励寻求/自我给药范式。这些初步的研究将确定在解决第二个和第四个目标时测量渴望相关行为的最佳参数。我们的第二个目标是测试药物寻找/口服自我给药过程，使用乙醇奖励，乙醇消耗小鼠C57Bl/6和抗渴望药物纳曲酮。第三个目标是在一种新型的力板运动分析仪中完成，目的是表征可卡因和安非他明对同一三种小鼠的致敏和条件药物效应。根据当代药物滥用理论，致敏性和条理性药物效应是导致成瘾和复吸的关键因素，我们利用力板传感器的初步数据表明，条理性药物效应和致敏性在空间和时间模式上都是可测量的。第四个主要目标是开发一种结合操作方法和力板传感器的混合装置，以便可以同时使用两种方法研究奖励寻求行为。为了实现第四个目标，将使用所有三种小鼠品系。在这些研究中，我们将应用最先进的计算机记录技术来测量涉及寻求奖励和自我给药的工具反应的物理特征，并量化菌株特异性致敏和条件药物反应。开发这样的动物模型，将提供一些必要的基本信息，以了解环境背景、遗传禀赋的个体差异和药理学变量如何影响药物渴望、药物寻求和最终药物服用。此外，未来使用这些方法的工作应该会导致更有效的临床前评估，以潜在有效的治疗和预防各种滥用药物的药物渴望策略。