Self-administration of abused inhalants in mice

小鼠滥用吸入剂的自我给药

基本信息

批准号：
6912477
负责人：
SCOTT E BOWEN
金额：
$ 2.25万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-04-01 至 2005-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Although the abuse of inhalants continues to be a significant public health problem throughout the U.S. and the world, there has been very little systematic examination of the reinforcing properties of these compounds. Therefore, the aim of this research proposal is to investigate and develop a method of inhalant self-administration that can be used long-term in mice to simulate the full array of human behaviors associated with solvent abuse including acquisition, maintenance, extinction and reinstatement of both inhalant-seeking and inhalant-taking behavior. This research will focus on the current hypothesis that a majority of the abused inhalants produce a profile of neurobehavioral effects that are analogous to those produced by abused depressant drugs (e.g. barbiturates, alcohol, benzodiazepines) [Evans and Balster, 1991]. A key objective of this research proposal is the design and implementation of a preclinical model of inhalant self-administration with a primary focus on the abused inhalants toluene and 1,1,1-trichloroethane. We are proposing two series of studies for this grant. In the first series, we propose to characterize the subjective and psychomotor effects of toluene and 1,1,1-trichloroethane and to compare them to other abused inhalants. The information collected from the first series of tests will then be used as a guide for our next series of studies. In the second series of studies, we propose to design and build an apparatus (i.e., a dynamic solvent delivery system interfaced with an operant monitoring system), which will reliably deliver a "dose" of inhalant on an intermittent basis. Once completed, we will use the system to develop and validate this method of solvent inhalation by training mice to press a lever for inhalant delivery and by varying both the "dose" of inhalant and the response requirements necessary for obtaining it. Finally, the research described in the present application will extend the knowledge base of psychomotor and subjective effects of abused inhalants. In addition, this research will have important implications for understanding basic mechanisms underlying and controlling inhalant abuse, for the development of treatment medications and behavioral techniques for modifying the abuse of inhalants.

描述（由申请人提供）：尽管滥用吸入剂仍在继续在美国和世界各地成为一个重大的公共卫生问题，对加强特性的系统检查很少这些化合物。因此，该研究建议的目的是调查和开发一种吸入自我管理的方法在小鼠中长期使用，以模拟与人类行为的全部相关行为通过溶剂滥用，包括获取，维护，灭绝和恢复寻求吸入的和吸入的行为。这研究将重点介绍当前大多数虐待的假设吸入剂产生的神经行为效应的特征与那些由滥用的抑郁剂药物（例如，巴比妥类药物，酒精，苯二氮卓类）[Evans and Balster，1991]。这项研究的关键目标建议是吸入临床前模型的设计和实施自我管理，主要关注滥用的吸入剂甲苯和 1,1,1-三氯乙烷。我们正在为这项赠款提出两项研究。在第一个系列中，我们建议表征主观和精神运动甲苯和1,1,1-三氯乙烷的影响，并将其与其他滥用吸入剂。从第一系列测试中收集的信息将然后用作我们下一系列研究的指南。在第二系列研究，我们建议设计和建造一种设备（即动态溶剂交付系统与操作监控系统连接），这将可靠地在间歇性的基础上可靠地提供吸入的“剂量”。完成后，我们将使用该系统开发和验证这种溶剂的方法通过训练小鼠吸入以向吸入输送和改变吸入剂的“剂量”和响应要求获得它。最后，本应用程序中描述的研究将扩展精神运动的知识基础和虐待的主观影响吸入剂。此外，这项研究将对了解和控制吸入滥用的基本机制，因为治疗药物和行为技术的开发修改滥用吸入剂。