CART:A novel cocaine regulated neurochemical

CART：一种新型可卡因调节的神经化学物质

• 批准号: 6607462
• 负责人: MICHAEL J KUHAR
• 金额: $ 41.47万
• 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 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6607462
• 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

In order to treat effectively and repair the disease of drug addiction, the critical mediators and defects in the brain must be known. While some mediators and defects or changes due to drugs are known, all the critical ones may not be fully known or understood. This proposal deals with a relatively new neurochemical that appears to play a role in the action of psychostimulant drugs such as cocaine and methamphetamine. This neurochemical is actually a small group of peptides referred to as CART peptides. They were discovered by giving animals cocaine or amphetamine, and CART peptides are found in many brain regions involved in reward and reinforcement. Moreover, some CART peptides, upon injection into the brain, produce effects that are psychostimulant-like suggesting that they may mediate, at least partly, some of the actions of these drugs. This proposal further characterizes the behavioral effects of CART peptides and explores the neurochemical and neuroanatomical bases for these effects. All known active CART peptides will be injected into brain regions associated with reward and reinforcement and it will be noted if they produce effects similar to those produced by psychostimulants. The interaction of CART peptides with cocaine and dopamine will be carefully analyzed. The precise location of endogenously occurring CART peptides will be delineated by light and electron microscopy in drug dependence-related neurocircuits. Taken together, these findings will substantially increase our knowledge of the role of CART peptides in the action of psychostimulant drugs, may enhance our understanding of the process of drug dependence, and may suggest targets for development of medications for psychostimulant abusers.

为了有效治疗和修复药物成瘾的疾病，必须知道大脑中关键的介体和缺陷。 尽管已知一些介质和缺陷或变化是已知的，但所有关键的介体可能并不完全了解或理解。 该建议涉及一种相对较新的神经化学，该神经化学似乎在可卡因和甲基苯丙胺等精神刺激药物的作用中起作用。 这种神经化学实际上是一小部分，称为CART肽。 它们是通过给动物可卡因或苯丙胺发现的，并且在许多涉及奖励和增强的大脑区域中发现了卡车肽。 此外，某些CART肽在注入大脑时会产生类似精神刺激性的作用，这表明它们至少可以部分介导这些药物的某些作用。 该建议进一步表征了Cart肽的行为效应，并探索了这些作用的神经化学和神经解剖学基础。所有已知的活跃的CART肽都将注入与奖励和增强相关的大脑区域，如果产生与精神刺激物相似的作用，则将注意到它们。 卡特肽与可卡因和多巴胺的相互作用将仔细分析。 内源性发生的CART肽的精确位置将通过与药物依赖性相关的神经环节中的光和电子显微镜描绘。综上所述，这些发现将大大提高我们对Cart肽在精神刺激药物作用中的作用的了解，可能会增强我们对药物依赖过程的理解，并可能提出针对精神刺激施用者的药物开发的靶标。