Neurobehavioral Assessment of Ethanol Seeking and Intake in the Rat

大鼠乙醇寻找和摄入的神经行为评估

基本信息

批准号：
8112588
负责人：
CRISTINE L CZACHOWSKI
金额：
$ 32.33万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8112588
关键词：
Accounting Affect Alcohol consumption Alcohol dependence Alcohols Amygdaloid structure Appetitive Behavior Behavior Behavioral Behavioral Model Blood alcohol level measurement Brain Cell Nucleus Cocaine Complex Consummatory Behavior Cues Development Dopamine Environment Ethanol Ethanol dependence Failure Future Glutamates Goals Human Individual Intake Learning Lesion Maintenance Modeling Motor Nucleus Accumbens Pathway interactions Performance Pharmaceutical Preparations Pharmacotherapy Phase Prefrontal Cortex Process Psychological reinforcement Publishing Rattus Regulation Reinforcement Schedule Research Research Personnel Resources Role Self Administration Self-Administered Site Specificity Stress Structure Sucrose Ventral Tegmental Area addiction alcohol availability alcohol reinforcement alcohol seeking behavior alcohol use initiation binge drinking drinking drug of abuse innovation motivated behavior neural circuit neurobehavioral neurochemistry programs psychostimulant reinforcer response

项目摘要

DESCRIPTION (provided by applicant): Alcohol acts as a potent reinforcer in humans and in rats, and the behaviors directly involved in alcohol use can be thought of as "goal-directed", involving two distinct phases: 1) the seeking or procurement of a particular resource (appetitive behaviors), and 2) the actual direct interactions with that resource (consummatory behaviors). This project utilizes an innovative behavioral model developed to separate the initial behavior required to obtain access to alcohol from the actual alcohol self-administration. Using this model, rats drink alcohol in the 1.0 g/kg range in <6 minutes, producing pharmacologically relevant blood alcohol concentrations (40-90mg%). Moreover, we have demonstrated that this model can identify drugs that specifically affect either the seeking or the drinking component of behavior while having little to no effect on the other component of alcohol-motivated responding. Thus, this approach provides a unique opportunity to examine the factors that independently and/or cooperatively affect the seeking and consumption of alcoholic beverages. The proposed studies systematically inactivate extremely localized neuroanatomical structures postulated to be involved in alcohol-seeking and intake, and then manipulate specific neurochemical function within these regions to dissect the neurocircuitry and neurochemistry underlying alcohol-motivated behavior. Overall, the project will: 1) assess alcohol-motivated behaviors where the preponderance of research on drug-seeking has been on other drugs of abuse; 2) focus on relatively discrete brain structures where many approaches necessitate less anatomical specificity; 3) examine alcohol vs. sucrose-reinforced responding to account for the regulation of behavior that is common to palatable, caloric goal substances; 4) lay the groundwork for the extension of the examination of binge drinking to the study of alcohol dependence; and 5) procedurally separate alcohol-seeking from drinking to attempt to identify the neuroanatomical and neurochemical substrates specific and common to these behaviors. The findings from this project will inform our basic understanding of the neural circuitry underlying alcohol-motivated behavior and determine whether or not this is a common reinforcement/addiction circuit or distinct to alcohol reinforcement. Importantly, these findings will also lay the groundwork for future pharmacotherapy development that can target an individual's specific dysregulation of seeking/initiation of drinking and/or failure to control drinking once begun.

描述（由申请人提供）：酒精充当人类和大鼠中的有效增强剂，直接参与饮酒的行为可以被视为“目标指导”，涉及两个不同的阶段：1）寻求或采购特定资源（胃部行为），以及2）与该资源的实际直接相互作用（2）与该资源的实际直接相互作用（Consummatimatory Condummatory Chandimatory）。该项目利用了开发的创新行为模型来将获得酒精访问所需的初始行为与实际的酒精自我管理所需的初始行为分开。使用此模型，大鼠在<6分钟内以1.0 g/kg的含量在1.0 g/kg的范围内饮酒，从而产生与药理学相关的血液酒精浓度（40-90mg％）。此外，我们已经证明，该模型可以识别出特殊影响行为的寻求或饮酒成分的药物，而对酒精动机的另一个组成部分几乎没有影响。因此，这种方法提供了一个独特的机会来检查独立和/或合作地影响酒精饮料的因素。拟议的研究系统地灭活了极端局部的神经解剖结构，这些结构被认为参与了寻求酒精和摄入量，然后在这些区域内操纵特定的神经化学功能，以剖析神经记录和神经化学的基础，从而剖析了酒精动机行为的基础。总体而言，该项目将：1）评估饮酒动机的行为，在这些行为中，关于毒品的研究占据了其他滥用药物； 2）专注于相对离散的大脑结构，许多方法需要较少的解剖特异性； 3）检查酒精与蔗糖增强的响应，以应对可口，热量目标物质的行为调节； 4）为扩大暴饮暴食的检查奠定了基础，以研究酒精依赖性； 5）在程序上，寻求酒精的饮酒与试图识别这些行为特定且共有的神经解剖学和神经化学底物。该项目的发现将为我们对酒精动机行为背后的神经回路的基本理解提供信息，并确定这是否是常见的增强/成瘾回路或与酒精增强的不同之处。重要的是，这些发现还将为未来的药物疗法开发奠定基础，以针对个人的特定失调，以寻求/或一旦开始饮酒，就可以控制饮酒。