Endogenous Opioid Systems Mediating Reward, Choice and Habit.

内源性阿片类药物系统调节奖励、选择和习惯。

• 批准号: 7283342
• 负责人: Nigel T Maidment
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7283342
• 关键词: Acute; Affect; Affective; Amygdaloid structure; Area; Arousal; Behavior; Behavioral; Behavioral Model; Brain; Brain region; Cannabinoids; Cell Nucleus; Cells; Chronic; Class; Condition; Corpus striatum structure; Cues; Development; Doctor of Philosophy; Dopamine; Endorphins; Enkephalins; Event; Gene Expression; Globus Pallidus; Goals; Habits; Knock-in Mouse; Knockout Mice; Laboratories; Learning; MCC protocol; Maps; Mediating; Mediator of activation protein; Microdialysis; Mitogen-Activated Protein Kinases; Modeling; Morphine; Mus; Naloxone; Nature; Neurons; Nucleus Accumbens; Opiates; Opioid; Opioid Peptide; Output; Pathology; Pharmaceutical Preparations; Population; Principal Investigator; Process; Psychological reinforcement; Rattus; Relapse; Research Personnel; Rewards; Role; Self Administration; Site; Stimulus; Structure; Substance P; Sucrose; System; Task Performances; abstracting; addiction; aversive conditioning; basal forebrain; classical conditioning; design; drug of abuse; endogenous cannabinoid system; endogenous opioids; hedonic; in vivo; preference; programs; receptor; research study; response; reward processing

Principal Investigator/Program Director (Last, First, Middle): Evans, Christopher J., Ph.D., Component III Component III: Endogenous Opioid Systems Mediating Reward, Choice and Habit. ABSTRACT: Endogenous opioid systems are considered important mediators of natural reward, as significant factors mediating acute and chronic responses to multiple abused drugs, and as potential regulators of affective state. However, whether endogenous opioids are solely "hedonic mediators" or are also involved directly in the reinforcement of responses to rewarding stimuli is unclear. The compulsive or habitual nature of drug- taking behavior is increasingly recognized as a major factor in addiction, and endogenous opioids may be key components of habit-forming circuitry. We will employ a battery of operant tasks in rats and in MOR-, DOR-, enkephalin- and B-endorphin-deficient mice designed to dissect the role of these components of opioid systems within specific basal forebrain regions, including the nucleus accumbens, ventral pallidum and amygdaloid nuclei, in mediating goal-directed versus habitual aspects of responses to natural rewards such as sucrose. Subsequently, we will identify the role of these specific opioid systems in the transition from flexible, goal-directed, reward seeking behavior to automatic habit-driven responding induced by repeated opiate exposure. Microdialysis will be used to provide evidence of opioid peptide release in such identified brain regions during performance of these tasks and on the influence of such release on dopamine release in dorsolateral striatum as a function of the transfer from flexible goal-directed reward seeking behavior to habitual responding. Since intact neurokinin and cannabinoid systems are reportedly required for opiate conditioned place preference and self-administration we will apply the same behavioral battery to Tac-1- and CB-1 KO mice to determine whether deficits lie in goal-directed or habitual aspects of responses to natural rewards in these models. In vivo phospho-MAP kinase responses to opiates will be compared to identify anatomical loci wherein opiate function is compromised. These studies will increase our understanding of factors underlying the transition from the controlled, deliberated pursuit of rewarding events, such as drugs of abuse, to compulsive drug-seeking, a key issue for the development of effective medications to treat addiction to multiple classes of abused substances. Primary

首席调查员/计划主管（最后，第一，中间）：埃文斯，克里斯托弗·J。 组件III：内源性阿片类系统介导奖励， 选择和习惯。 抽象的： 内源性阿片类药物系统被认为是自然奖励的重要介体，这是重要因素 介导对多种滥用药物的急性和慢性反应，并作为情感的潜在调节剂 状态。但是，内源性阿片类药物是仅仅是“享乐主义者”还是直接参与 尚不清楚对奖励刺激的反应的加强。药物的强迫性或习惯性 - 采取行为越来越被认为是成瘾的主要因素，内源性阿片类药物可能是 习惯性电路的关键组成部分。我们将在大鼠和Mor-中采用一系列操作任务 dor-，nkephalin-和b-内啡肽缺乏小鼠，旨在剖析这些成分的作用 特定基础前脑区域内的阿片类药物系统，包括伏隔核，腹侧pallidum 和杏仁核核，在介导的目标定向与自然奖励反应的习惯方面 例如蔗糖。随后，我们将确定这些特定阿片类药物在过渡中的作用 从灵活的，目标指导的寻求行为到自动习惯驱动的反应 重复鸦片暴露。微透析将用于提供此类阿片类肽释放的证据 在这些任务执行过程中确定了大脑区域以及此次释放的影响 背外侧纹状体中的多巴胺释放，这是从灵活目标指导奖励转移的函数 寻求行为以进行习惯回应。据报道，由于完整的神经激素和大麻素系统是 鸦片条件条件的地方偏好和自我管理所需的我们将采用相同的行为 电池到TAC-1-和CB-1 KO小鼠，以确定缺陷是否在于目标定向或习惯性方面 在这些模型中对自然奖励的回应。体内磷酸化映射激酶对阿片类药物的反应将是 比较确定解剖基因座，其中鸦片功能受到损害。 这些研究将增加我们对从受控，， 经过审议的奖励事件（例如滥用毒品）进行强迫性毒品，这是一个关键问题 为了开发有效的药物来治疗多种类别的滥用物质。 基本的