Rapid DA-Acb signaling in ingestive behaviors

摄取行为中的快速 DA-Acb 信号传导

• 批准号: 6816915
• 负责人: MITCHELL F ROITMAN
• 金额: $ 10.58万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-10 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6816915
• 关键词: appetite; avoidance behavior; bioimaging /biomedical imaging; brain imaging /visualization /scanning; dopamine; food flavor; laboratory rat; leptin; microelectrodes; neural transmission; nucleus accumbens; nutrient intake activity; reinforcer; sectioning; stimulus /response; taste

DESCRIPTION (provided by applicant): The rapid, subsecond signaling of the neurotransmitter dopamine (DA) and neurons in the nucleus accumbens (Acb) have been strongly implicated in cocaine seeking behaviors and drug taking in general. This Career Development Award will characterize the innate responses of DA and Acb cell firing to natural stimuli and how the responses change as a function of learning, motivation and endogenous peptide action. The award will also serve to train the PI in state-of-the-art electrophysiological and electrochemical techniques while he establishes his own independent line of research. In Experiements 1-3, DA and Acb activity will be rapidly sampled in two groups of animals using: 1) in vivo fast-scan cyclic voltammetry at carbon-fiber micrelectrodes (to measure subsecond increases in extracellular Acb DA) and 2) using chronically implanted microwire electrode arrays (to measure the electrophysiological activity of Acb neurons). In Experiement 1, the rapid responses of this system to rewarding (sucrose) and aversive (quinine) taste stimuli will be assessed in naive, untrained rats. In Experiment 2, the role of this system in learning cue-tastant associations will be determined by assaying it before, during and after classical conditioning of environmental stimuli to rewarding (sucrose) or aversive (quinine) tastant delivery. In Experiment 3, the integration of motivated state by this neural system will be assessed by recording rapid responses to the taste of a hypertonic sodium solution in rats with (rewarding) or without (aversive) a sodium appetite. In Experiment 4, the impact of peptides that affect food intake (leptin, melancortins) on rapid DA signaling in the Acb will be determined in an in vitro brain slice preparation. Effects of these peptides on rapid DA release would strongly support investigation of the use of these peptides not just in the treatment of obesity but in the treatment of drug addiction as well. These studies will establish the range of natural stimuli that promote rapid DA-Acb signaling - setting the foundation for examining aberrant signaling underlying drug addiction.

描述（由申请人提供）： 神经递质多巴胺（DA）和神经元在伏隔核（ACB）中的快速，超代信号传导与可卡因寻求行为和药物一般服用的强烈涉及。该职业发展奖将表征DA和ACB细胞对自然刺激的天生反应，以及对学习，动机和内源性肽作用的函数的反应如何变化。该奖项还将在他建立自己的独立研究系列的同时，以最先进的电生理和电化学技术来培训PI。在经验1-3中，将在两组动物中快速采样DA和ACB活性：1）使用：1）在碳纤维微电极上的体内快速扫描循环伏安法（测量细胞外ACB DA中的亚次升高），并使用长期植入的Microwire Electrode Electrode阵列（测量ACB neurons and acb neurons and aCB neurons）使用ACB neurons的活性。在经验1中，将在幼稚的未经训练的大鼠中评估该系统对奖励（蔗糖）和厌恶（奎宁）味觉刺激的快速响应。在实验2中，该系统在学习提示 - 与之相关联的作用将通过在环境刺激的经典条件之前，之中和之后确定，以奖励（蔗糖）或厌恶（quinine）味道味。在实验3中，通过记录对（奖励）或没有（厌恶）钠食欲的大鼠中高渗钠溶液的味道的快速反应来评估该神经系统动机状态的整合。在实验4中，将在体外脑切片制剂中确定影响食物摄入量（瘦素，梅兰科蛋白）对ACB快速DA信号传导的影响。这些肽对快速DA释放的影响将强烈支持对这些肽的使用不仅在肥胖治疗中，而且还在治疗药物成瘾方面。这些研究将建立促进快速DA -ACB信号传导的自然刺激范围 - 为检查基础药物成瘾的异常信号的基础奠定了基础。