CORE--BEHAVIORAL

项目资助研究已经确定了几种信号蛋白 调节对滥用药物的行为反应， 受到慢性药物暴露的影响行为核心的目的是 提供一个高通量的行为屏幕来描述角色 在一些相对简单的药物中发挥作用 相关行为被认为是药物成瘾的模型。在 在这些研究中，感兴趣的蛋白质将通过以下方式调节：1）通过 脑内注射激活剂或抑制剂; 2）通过直接 用过表达蛋白质的病毒载体转染神经元 或3）通过使用缺乏或过表达所述基因的遗传突变小鼠， 目的蛋白（参见转基因核心）。调节的影响 然后在以下一种或多种中测试靶蛋白 行为模型：1）首次用药动物的新奇寻求行为， 被认为预测并可能导致个体差异的特征 在药物滥用中; 2）可卡因或吗啡的运动敏感性， 神经可塑性被认为是由大脑中的神经可塑性引起的行为现象 反复暴露于药物滥用后的中脑边缘多巴胺系统; 3)阿片类药物的身体戒断，其中特定的行为被认为是 反映了阿片类药物依赖在离散脑中的神经适应 区域，包括蓝斑;和4）位置条件反射， 可卡因或吗啡，这提供了一个间接的奖励措施， 药物暴露初期的影响，以及条件作用的地方， 阿片类药物依赖动物的厌恶， 阿片类药物戒断的后果;这两种行为被认为涉及 丘脑核和相关边缘系统中的神经传递改变 结构. 因此，行为核心将为个人提供调查人员， 此补助金的项目与一个剧目的行为测定。目标是 使研究人员能够将分子和细胞现象 这构成了我们研究计划的基础， 与药物成瘾相关的功能相关行为终点。 最终，将在本研究中研究较少数量的分子事件。 更复杂的自我给药、复发和 有条件的加固，形成项目4的基础。通过 在这个核心中整合更多的常规行为分析，我们确保 分析的质量控制和将行为 在一个项目的调查结果到另一个，以及促进一体化 分子，细胞和行为水平的分析，主要是 我们的计划项目赠款的目标。

Program Project Grant research has identified several signaling proteins that modulate behavioral responses to drugs of abuse or are themselves modulated by chronic drug exposure. The purpose of the Behavioral Core is to provide a high-throughput, behavior screen to characterize the role played by these proteins in several relatively straightforward drug- related behaviors that are thought to model aspects of drug addiction. In these studies, a protein of interest will be modulated by 1) by intracerebral injection of activators or inhibitors; 2) by direct transfection of neurons with viral vectors over expressing the protein of interest; or 3) by using genetic mutant mice that lack or over express the protein of interest (see Transgenic Core). The effects of modulating the target protein will then be tested in one or more of the following behavioral models: 1) novelty-seeking behavior in drug-naive animals, a trait thought to predict and perhaps contribute to individual differences in drug abuse; 2) locomotor sensitization to cocaine or morphine, a behavioral phenomenon thought to result from neuroplasticity in the mesolimbic dopamine system following repeated exposure to drugs of abuse; 3) opiate physical withdrawal, where specific behaviors are thought to reflect the neuroadaptations of opiate dependence in discrete brain regions, including the locus coeruleus; and 4) place conditioning to cocaine or morphine, which provides an indirect measure of the rewarding effects of initial periods of drug exposure, as well as conditioned place aversion in opiate-dependent animals, which measures the aversive consequence of opiate withdrawal; both behaviors are thought to involve altered neurotransmission in the nucleus accumbens and related limbic structures. The Behavioral Core will thereby provide investigators in the individual Projects of this grant with a repertoire of behavioral assays. The goal is to enable investigators to relate the molecular and cellular phenomena that form the foundation of our program of research to specific and functionally relevant behavioral endpoints related to drug addiction. Ultimately, a smaller number of molecular events will be studied in the more complex behavioral models of drug self-administration, relapse, and conditioned reinforcement that form the basis of Project 4. By consolidating more routine behavioral assays in this Core, we ensure quality control of the assays and the ability to relate behavioral findings in one Project to another, as well as facilitate the integration of molecular, cellular, and behavioral levels of analysis, a major objective of our Program Project Grant.