Neurobehavioral Assessment of Ethanol Seeking and Intake

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 酒精消费，并为申请人的研究生涯做好准备 整合了不同的研究领域。饮酒可以是 被概念化为涉及两个阶段的行为。首先，在一定程度上 达到动机或“渴望”时，一个人很可能会 找点酒喝。其次，一旦饮酒开始，额外的因素决定了 那场饮酒大赛要喝多少。行为的两个阶段 有助于全面规范酒精摄入量：第一个决定 消费的时间和频率决定了消费的数量 每次的酒精摄入量。目前使用的动物模型主要集中在 关于第二阶段的行为。这项拟议的研究利用了一种新的 开发了将酗酒和酗酒区分开来的行为范式 自治。这个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的特征。第一，解决方案的效果 两种类型的行为的组合将通过操作 提供的乙醇和蔗糖溶液的浓度。 第二，动物当前的动机状态在 已经摄取的溶液的量将通过不同的 在寻找机会之前给予的蔗糖或乙醇的量 并使用额外的解决方案。目标1将采用行为方法来 了解乙醇自我给药行为并建立在当前 申请人的技能。该项目的目标2是评估 5-羟色胺在中皮质边缘环路中的作用 这个模型中的饮酒行为。据推测，中国的变化 5-羟色胺活性影响酒精诱导的行为 背中缝，含5-羟色胺的主要细胞体的位置 腹侧被盖区(VTA)和伏隔核。AIM 2用途 中缝背侧核、VTA和核内定位微量注射 伏隔和5-羟色胺IA和IB激动剂的给药 5-羟色胺输入在控制酒精饮酒中的作用。这 一系列实验构成了该项目的大部分，并将涉及 对申请者进行广泛的药理学和神经科学方面的培训 酒精自控。作为一个整体，该项目将允许 酒类消费分析的综合方法：比较 由于操纵溶液组成而产生的行为， 受试者的动机状态和潜在的神经机制。

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.