Psychostimulant-like effects of CART neuropeptides

CART 神经肽的类似精神兴奋作用

• 批准号: 6583862
• 负责人: JASON N JAWORSKI
• 金额: $ 3.83万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-10-01 至 2005-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6583862
• 关键词: amphetamines; cocaine; dopamine; dopamine receptor; drug addiction; genetic transcription; high performance liquid chromatography; laboratory rat; microdialysis; neurons; neuropeptides; nucleus accumbens; substance abuse related behavior

DESCRIPTION (provided by applicant): Cocaine and amphetamine regulated transcript (CART) peptide is an endogenous peptide which appears to have psychostimulant-like properties and may be involved in the actions of cocaine and other psychostimulants. Understanding the effects of CART peptide is important because it will give insight into the addiction process and will contribute to the goal of developing a pharmacological treatment for cocaine and amphetamine addiction. The purpose of this study is to more fully characterize the behavioral and neurochemical psychostimulant-like actions of CART peptide and its interaction with cocaine. This includes determining 1) if behavioral sensitization or tolerance occurs to repeated CART injections and if cross-sensitization occurs to cocaine; 2) if CART injection into the ventral tegmental area and nucleus accumbens increases extracellular dopamine concentrations in the nucleus accumbens like psychostimulants do; and 3) if CART can modify cocaine self-administration. The researchers hypothesis is that CART will act in a similar manner as cocaine on these measures. By studying the behavioral and neurochemical effects of CART and it's interactions with cocaine, this project will yield a greater understanding of both the acute reinforcing mechanisms of cocaine and long-term changes that occur during chronic cocaine abuse. A greater understanding of the functions of CART may in turn lead to novel treatment strategies for psychostimulant abuse.

描述（由申请人提供）： 可卡因和苯丙胺调节转录物（CART）肽是一种内源性肽，具有精神兴奋剂样性质，可能参与可卡因和其他精神兴奋剂的作用。了解CART肽的作用很重要，因为它将使人们深入了解成瘾过程，并有助于开发可卡因和苯丙胺成瘾的药理学治疗方法。本研究的目的是更全面地描述CART肽的行为和神经化学精神兴奋剂样作用及其与可卡因的相互作用。这包括确定1）是否对重复的CART注射发生行为敏化或耐受，以及是否对可卡因发生交叉敏化; 2）是否将CART注射到腹侧被盖区和丘脑核中增加丘脑核中的细胞外多巴胺浓度，就像精神兴奋剂一样;以及3）CART是否可以改变可卡因自我给药。研究人员假设，CART在这些措施上的作用与可卡因类似。通过研究CART的行为和神经化学作用及其与可卡因的相互作用，该项目将更好地了解可卡因的急性强化机制和慢性可卡因滥用期间发生的长期变化。对CART功能的更深入了解可能反过来导致精神兴奋剂滥用的新治疗策略。