CART--A NOVEL COCAINE REGULATED NEUROCHEMICAL

CART--一种新型可卡因调节神经化学物质

• 批准号: 6125030
• 负责人: MICHAEL J KUHAR
• 金额: $ 20.56万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-15 至 2001-07-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6125030
• 关键词: Primates; SDS polyacrylamide gel electrophoresis; amphetamines; animal genetic material tag; brain; brain mapping; cocaine; cyclic AMP; drug abuse; drug addiction; drug interactions; drug receptors; electron microscopy; genetically modified animals; human tissue; immunocytochemistry; in situ hybridization; laboratory mouse; microinjections; neurochemistry; northern blottings; peptide chemical synthesis; radioimmunoassay; self medication; videotape /videodisc; western blottings

DESCRIPTION (Applicant's Abstract): Cocaine amphetamine, and other psychostimulant drugs, cause abuse and addiction by interacting with and altering certain neurochemical systems in brain. Recently, a neurochemical has been discovered which appears to be involved in cocaine's action. This neurochemical has been named CART (fro Cocaine and Amphetamine Regulated Transcript). The goal of this proposal is to clarify how CART peptides mediate or modulate the effects of cocaine and other psychostimulant drugs. A first step in this work is to show that injection of these peptides into the brain causes the same physiological effects that are caused by cocaine. In other words, CART peptides cause increased locomotor activity in rodents and reduced food intake. These are well known effects of the psychostimulant drugs themselves. In addition, we will look at the effects of these drugs at brain receptors; stimulation of physiologic receptors in brain is known to produce second messengers molecule such as cyclic AMP. Further, we will map the distribution of CART peptides in brain so as to fully understand where they are located and how they might influence the brain. We will also look at the effects of blocking their production and availability so as to obtain additional evidence about what they do, and we will prepare to make transgenic mice which either overproduce or have no CART peptide. These experiments will help us to understand how cocaine changes the brain, will show us how these new neurochemicals, the CART peptides, are involved in drug abuse, and may provide new strategies for developing medications to treat cocaine abuse and dependence.

描述（申请人的摘要）： 可卡因苯丙胺和其他精神刺激药物会造成滥用和 通过与某些神经化学系统互动并改变成瘾 脑。 最近，已经发现了一种神经化学 参与可卡因的行动。 这种神经化学被命名为购物车（来回 可卡因和苯丙胺调节的转录本）。 该提议的目的是 为了阐明卡特肽如何介导或调节可卡因和可卡因的影响 其他精神刺激药物。 这项工作的第一步是表明将这些肽注射到 大脑会引起与可卡因相同的生理作用。 换句话说，卡特肽会导致啮齿动物的运动活性增加 减少食物摄入量。 这些是众所周知的效果 精神刺激药物本身。 此外，我们将研究效果 这些药物在大脑受体中；刺激生理受体 已知大脑会产生第二个使者分子，例如环状AMP。 此外，我们将绘制大脑中的Cart肽的分布，以便 完全了解它们的位置以及它们如何影响 脑。 我们还将研究阻止其产量的影响 可用性以获取有关他们所做工作的其他证据，我们 将准备制作过量生产或没有的转基因小鼠 推车肽。 这些实验将帮助我们了解可卡因如何改变大脑， 将向我们展示这些新的神经化学物质（Cart肽）如何涉及 在药物滥用方面，可能会为开发药物提供新的策略 治疗可卡因滥用和依赖。