Ethopharmacological Characterization of Reward Systems

奖励系统的民族药理学特征

• 批准号: 6822863
• 负责人: Robert Huber
• 金额: $ 13.9万
• 依托单位: BOWLING GREEN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6822863
• 关键词: alternatives to animals in research; amines; amphetamines; behavioral /social science research tag; behavioral habituation /sensitization; cocaine; crayfish; disease /disorder model; drug addiction; ethology; hemolymph; invertebrate locomotion; microdialysis; microinjections; model design /development; neurochemistry; reinforcer; self medication; substance abuse related behavior; videotape /videodisc

DESCRIPTION (provided by applicant): Models of addiction have been essential for uncovering the neurobiological factors associated with drug-seeking behavior. In addition to the use of typical mammalian models, development of simplified systems for the study of addiction may contribute significant new experimental opportunities for an analysis of widely conserved underlying neural processes. The increased inclusion of invertebrate models for the study of fundamental phenomena is also consistent with current goals and guidelines in the ethics of animal use. In recent work, we have demonstrated that drugs of abuse are associated with rewarding properties for place-conditioning in crayfish. The experimental advantages of crayfish include a relatively simple and accessible CNS organization, and sets of conspicuous, stereotyped behavior patterns amenable to effective quantitative analysis. This grant aims to develop initial findings into a robust model for the study of drug-reward with a characterization (1) of drug-induced changes in locomotion and amine hemolymph release, (2) of sensitization and dose-response relationships in a place conditioning paradigm, and (3) of an automated, operant self-administration paradigm. Successful completion will allow us to advance a novel experimental system of drug-reward. With multiple levels of organization readily accessible, a detailed characterization of this intriguing behavioral phenomenon in a species not particularly known for its cognitive abilities will provide a unique, comparative ethological perspective on the neural substrates responsive to drugs of abuse, the nature of reward mechanisms, drug-seeking, and motivated behaviors in general. In sum, the continued development of novel experimental paradigms, such as those described here, promise to provide new insights into the evolutionarily derived neurochemical systems from which human drug addictions stem.

描述（由申请人提供）：成瘾模型对于发现与寻求药物行为相关的神经生物学因素至关重要。除了使用典型的哺乳动物模型外，开发成瘾研究的简化系统可能为分析广泛保守的基础神经过程的分析提供了重要的新实验机会。纳入基本现象研究的无脊椎动物模型的纳入也与动物使用伦理方面的当前目标和准则一致。在最近的工作中，我们证明了滥用药物与小龙虾中的地点条件有关。小龙虾的实验优势包括一个相对简单且可访问的中枢神经系统组织，以及一组引人注目的，刻板印象的行为模式，可符合有效的定量分析。该赠款旨在将初步发现发展为一个强大的模型，以研究药物奖励的研究（1），其表征（1）是药物诱导的运动变化和胺血淋巴释放的变化，（2）在调节范式中的敏化和剂量反应关系的（2），以及（3）的自动化，操作，操作自动化自动化自动化范式。成功的完成将使我们能够推进一种新型的药物奖励实验系统。随着多个组织的多个级别的易于访问，对这种有趣的行为现象的详细表征在不特别以其认知能力而闻名的物种中，将为对滥用药物的响应，奖励机制，吸毒和激励行为的性质的神经底物提供独特的，比较的伦理学观点。总而言之，新型实验范式的持续发展（例如此处描述的）有望提供有关人类药物成瘾源于进化的神经化学系统的新见解。