Psychostimulant-like effects of CART neuropeptides

描述(由申请人提供)： 可卡因和苯丙胺调节转录肽(CART)是一种内源性多肽，具有精神刺激物的性质，可能参与可卡因和其他精神刺激物的作用。了解CART肽的作用很重要，因为它将使我们深入了解成瘾过程，并将有助于开发治疗可卡因和苯丙胺成瘾的药物疗法的目标。本研究的目的是更全面地表征CART多肽的行为和神经化学类心理刺激作用及其与可卡因的相互作用。这包括确定1)重复注射CART是否发生行为敏化或耐受性，以及可卡因是否发生交叉敏化；2)CART注射到腹侧被盖区和伏隔核是否像精神刺激剂那样增加伏隔核细胞外多巴胺浓度；以及3)CART是否可以改变可卡因的自我给药。研究人员假设，在这些指标上，CART的作用方式与可卡因类似。通过研究CART的行为和神经化学效应及其与可卡因的相互作用，该项目将更好地理解可卡因的急性强化机制和慢性可卡因滥用过程中发生的长期变化。对CART功能的更好理解可能反过来导致针对精神刺激性虐待的新的治疗策略。

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.