DRUGS OF ABUSE AND BRAIN STIMULATION REWARD IN THE MOUSE

滥用药物和小鼠大脑刺激奖励

• 批准号: 6515892
• 负责人: CONAN KORNETSKY
• 金额: $ 16.3万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-15 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6515892
• 关键词: cocaine; dopamine receptor; dopamine transporter; drug abuse; gene targeting; genetically modified animals; laboratory mouse; morphine; psychopharmacology; reinforcer

DESCRIPTION (provided by applicant): In recent years a Major thrust in the study of the characteristics of the drug abuser has focused on vulnerability, the possible role that genetics play in this vulnerability, and the molecular underpinnings of the mechanisms of use and relapse into drug use. Intrinsic to the understanding of these problems is the understanding of the mechanisms involved in the action of the abused substances on the brain reward system(s). However, for the most part, researchers have made use of the rat as the animal of choice for study, while most of the experiments on genetic differences make use of mouse as the experimental animal. In trying to investigate the behavior of these genetic mutations investigators have relied mostly on simple unconditioned behavior. The proposed research is designed to adapt for the mouse techniques for measuring the changes in brain-stimulation reward (BSR) that have been successfully used in the rat. The procedures are 1) a discrete trial, rate independent, psychophysical method for measuring the BSR threshold and 2) a parallel procedure that measures the ability of the animal to attend to a stimulus by measuring the detection of non-rewarding stimulation from the same brain site. In addition to measuring the stimulation thresholds, latency of response is also measured. Thus the techniques allow for the determination of not only changes in the reward system but also whether these changes are confounded by motor and attention factors. The proposed experiments will explore differences in response to morphine and cocaine in CB57/B6 and D, and DAT deficient mutant mice. Successful development of these procedures in mice will allow a more specific understanding of the nature of specific phenotypes that may have relationships to the human condition.

描述（由申请人提供）：近年来 对滥用药的特征的研究集中在脆弱性上， 遗传学在这个脆弱性和分子中的可能作用 使用和复发到药物使用机制的基础。固有的 对这些问题的理解是对机制的理解 参与滥用物质对大脑奖励系统的作用。 但是，在大多数情况下，研究人员将大鼠用作动物 研究的选择，而大多数关于遗传差异的实验使得 使用小鼠作为实验动物。试图调查行为 这些遗传突变研究者主要依赖于简单 无条件的行为。拟议的研究旨在适应 测量脑刺激奖励变化（BSR）的鼠标技术（BSR） 已成功用于大鼠。程序为1）离散 试验，率独立的心理物理方法，用于测量BSR阈值 2）一个平行程序，可以衡量动物参加的能力 通过测量从刺激中的刺激 同一大脑部位。除了测量刺激阈值外，等待 还测量了响应。因此，这些技术允许确定 不仅在奖励系统中变化，还包括这些更改 被运动和注意因素混淆。提出的实验将 探索CB57/B6和D中对吗啡和可卡因的响应差异，以及 DAT缺陷突变小鼠。这些程序在小鼠中的成功开发 将允许对特定表型的性质有更具体的理解 这可能与人类状况有关系。