Ethopharmacological Characterization of Reward Systems

奖励系统的民族药理学特征

• 批准号: 6953622
• 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/6953622
• 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）：成瘾模型对于揭示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之外，开发用于成瘾研究的简化系统可能会为分析广泛保守的潜在神经过程提供重要的新实验机会。越来越多地使用无脊椎动物模型来研究基本现象也符合当前动物使用伦理的目标和准则。在最近的工作中，我们证明了滥用药物与小龙虾的环境调节的奖励特性有关。小龙虾的实验优势包括相对简单且易于理解的中枢神经系统组织，以及一系列明显的、刻板的行为模式，可以进行有效的定量分析。该赠款旨在将初步发现发展成一个强大的药物奖励研究模型，其特征在于（1）药物引起的运动变化和胺血淋巴释放，（2）场所调节中的敏化和剂量反应关系范式，以及（3）自动化的、可操作的自我管理范式。成功完成将使我们能够推进一种新颖的药物奖励实验系统。由于可以容易地获得多个层次的组织，对一个不以其认知能力而闻名的物种中这种有趣的行为现象的详细描述将为对滥用药物、奖励机制的性质、寻求毒品和一般动机行为。总之，新的实验范式的持续发展，例如这里描述的那些，有望为人类毒瘾起源的进化神经化学系统提供新的见解。