Neurobehavioral Assessment of Ethanol Seeking and Intake

乙醇寻求和摄入的神经行为评估

• 批准号: 6369813
• 负责人: CRISTINE L CZACHOWSKI
• 金额: $ 11.19万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-27 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6369813
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; appetite; behavioral /social science research tag; craving; dopamine; dorsal raphe nucleus; ethanol; laboratory rat; microinjections; neural information processing; neuroanatomy; neuropsychological tests; neuropsychology; neuroregulation; nucleus accumbens; prefrontal lobe /cortex; psychological models; psychophysiology; self medication; serotonin; serotonin inhibitor; substance abuse related behavior; sucrose; tegmentum

DESCRIPTION (provided by applicant): This project adopts a multidisciplinary approach, combining behavioral analyses and neuroscience techniques, to determine factors that regulate alcohol consumption and to prepare the applicant for a research career that integrates different fields of study. Alcohol consumption can be conceptualized as involving two phases of behavior. First, some level of motivation or "Craving" is reached that makes it likely that a person will seek out alcohol. Second, once the drinking has begun, added factors determine how much will be consumed in that drinking bout. Both phases of behavior contribute to the overall regulation of alcohol intake: the first determines the timing and frequency of consumption and the second determines the amount of alcohol intake at each time. Animal models currently in use primarily focus on the second phase of behavior. The proposed research makes use of a newly developed behavioral paradigm that separates alcohol seeking from self-administration. The first specific Aim of this project is to continue to characterize these two behaviors in this model. First, the effects of solution composition on the two types of behavior will be assessed by manipulating the concentrations of the ethanol and sucrose solutions that are presented. Second, the importance of the current motivational state of the animal in terms of the amount of solution already ingested will be measured by varying the amount of sucrose or ethanol administered prior to an opportunity to seek and consume additional solution. Aim 1 will employ a behavioral approach to understanding ethanol self-administration behavior and builds upon the current skills of the applicant. Aim 2 of the project is to assess the role of serotonin in the mesocorticolimbic circuitry as it affects the two phases of drinking behavior in this model. It is hypothesized that alterations in serotonin activity affect ethanol-directed behaviors via projections from the dorsal raphe, the location of the main serotonin-containing cell bodies, to the ventral tegmental area (VTA) and the nucleus accumbens. Aim 2 uses site-specific microinjections into the dorsal raphe, the VTA and the nucleus accumbens and the administration of serotonin IA and IB agonists to determine the role of this serotonin input in the control of ethanol drinking. This series of experiments makes up the majority of the project, and will involve extensive training for the applicant in the pharmacology and neuroscience of alcohol self-administration. The project as a whole will allow for an integrated approach to the analysis of alcohol consumption: the comparison of behaviors that result from manipulations of solution composition, the motivational state of the subjects and underlying neural mechanisms.

描述（由申请人提供）： 该项目采用多学科方法，结合行为学 分析和神经科学技术，以确定调节因素 饮酒并为申请人的研究生涯做好准备 整合了不同的研究领域。饮酒量可以 概念化为涉及行为的两个阶段。首先，一定程度的 动机或“渴望”的达到使得一个人可能会 寻找酒精。其次，一旦开始饮酒，其他因素就决定了 在那场饮酒比赛中会消耗多少。两个阶段的行为 有助于酒精摄入的整体调节：首先决定 消费的时间和频率，第二个决定数量 每次的酒精摄入量。目前使用的动物模型主要关注 关于第二阶段的行为。拟议的研究利用了新的 开发了将酗酒与酗酒区分开来的行为范式 自我管理。该项目的第一个具体目标是继续 在此模型中描述这两种行为。一、解决方案效果 两种行为的构成将通过操纵来评估 所呈现的乙醇和蔗糖溶液的浓度。 其次，动物当前动机状态的重要性 已经摄入的溶液量将通过不同的方法来测量 在寻求机会之前施用的蔗糖或乙醇的量 并消耗额外的溶液。目标 1 将采用行为方法 了解乙醇自我管理行为并建立在当前的基础上 申请人的技能。该项目的目标 2 是评估 中皮质边缘回路中的血清素，因为它影响大脑的两个阶段 该模型中的饮酒行为。据推测，改变 血清素活性通过预测影响乙醇导向的行为 中缝背侧，主要含血清素细胞体的位置， 腹侧被盖区（VTA）和伏隔核。目标2用途 中缝背侧、VTA 和细胞核的位点特异性显微注射 伏隔核和血清素 IA 和 IB 激动剂的施用以确定 这种血清素输入在控制乙醇饮酒中的作用。这 系列实验构成了该项目的大部分内容，并将涉及 为申请人提供药理学和神经科学方面的广泛培训 酒精自我管理。该项目作为一个整体将允许 酒精消费分析的综合方法：比较 由溶液成分的操纵导致的行为， 受试者的动机状态和潜在的神经机制。