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 分析和神经科学技术，以确定调节 酒精消费，并准备申请人的研究生涯， 融合了不同的研究领域。酒精消费可以 被概念化为涉及行为的两个阶段。第一，某种程度的 动机或“渴望”达到，使一个人很可能会 寻找酒精。第二，一旦开始饮酒， 在这场饮酒比赛中会消耗多少行为的两个阶段 有助于酒精摄入量的整体调节：第一个决定 消费的时间和频率，第二个决定了消费的数量 酒精的摄入量。目前使用的动物模型主要集中在 行为的第二阶段。这项研究利用了一种新的 发展出一种行为模式， 自我管理。该项目的第一个具体目标是继续 在这个模型中描述这两种行为。第一，解决方案的效果 两种行为的组合将通过操纵 所呈现的乙醇和蔗糖溶液的浓度。 第二，动物当前的动机状态在 已经摄入的溶液量的术语将通过改变 在寻找机会之前给予的蔗糖或乙醇的量 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 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5-羟色胺，因为它影响两个阶段， 在这个模型中的饮酒行为。据推测， 5-羟色胺活性影响乙醇导向的行为，通过预测从 中缝背侧，主要含胡萝卜素的细胞体的位置， 腹侧被盖区（VTA）和延髓核。Aim 2用途 在中缝背核、腹侧被盖区和核中进行特定部位的显微注射 本发明的组合物和5-羟色胺IA和IB激动剂的施用以确定 这种血清素输入在控制酒精饮用中的作用。这 一系列的实验构成了该项目的大部分，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： 行为的结果，从操纵的解决方案组成， 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.