Alcohol Vapor Self-Administration in Rats

大鼠酒精蒸气自我管理

基本信息

批准号：
10201412
负责人：
Olivier George
金额：
$ 35.55万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10201412
关键词：
Abstinence Accidental Injury Acute Alcohol consumption Alcohol dependence Alcohol withdrawal syndrome Alcoholic Intoxication Alcoholism Alcohols Animal Model Animals Behavior Blood alcohol level measurement Brain Mapping Brain region Chronic Conscious Consumption Corpus striatum structure Cues Data Deltastab Dependence Development Ethanol Ethanol dependence Event Exhibits Exposure to FDA approved Female Funding Gold Grant Hour Human Hyperalgesia Impairment Maintenance Mediating Memory Memory Loss Modeling Motivation National Institute on Alcohol Abuse and Alcoholism Neurons Neuropharmacology Performance Pharmaceutical Preparations Policies Rattus Reinforcement Schedule Relapse Risk Rodent Self Administration Series Sex Differences Sexually Transmitted Diseases Short-Term Memory Strategic Planning Stress Techniques Testing Volition Withdrawal Work addiction adverse outcome alcohol effect alcohol exposure alcohol pharmacology alcohol poisoning alcohol relapse alcohol use disorder anxiety-like behavior base binge drinking clinically relevant design high intensity drinking male neuronal circuitry novel novel therapeutic intervention recruit sexual assault vapor

项目摘要

Project Summary / Abstract A major issue in the alcohol field is the lack of animal models of the voluntary induction and maintenance of alcohol dependence. Rats will readily self-administer alcohol, but the amount of alcohol consumed is very low and thus does not produce blood alcohol levels that are clinically relevant for alcoholism (100-200 mg% for several hours per day). In the previous funding period, we successfully developed a novel model of the voluntary induction and maintenance of alcohol dependence in rats using chronic intermittent ethanol vapor self- administration (EVSA). In this model, animals exhibit severe addiction-like behaviors, including somatic signs of withdrawal, anxiety-like behavior, hyperalgesia, and responding despite adverse consequences (on a progressive-ratio schedule of reinforcement) after 6 weeks of EVSA. The current proposal seeks to further develop this paradigm, identify the neuronal networks of the voluntary induction of alcohol dependence, and characterize a novel model of voluntary “extreme binging.” Extreme alcohol binging is a critical societal issue and one of the priorities of the NIAAA Strategic Plan 2017-2021. Binge and extreme binge drinking are particularly troubling because they increase the risks for blackouts, alcohol poisoning, sexual assault, sexually transmitted diseases, poor academic performance, and developing AUD. By combining alcohol vapor self- administration with state-of-the-art brain mapping techniques, we will identify neuronal networks that drive alcohol drinking and relapse after the voluntary induction of alcohol dependence. Our data show that both the passive and active administration of alcohol vapor produces the escalation of alcohol drinking, increases the motivation to obtain alcohol, and increases relapse, but the voluntary induction of dependence is characterized by the specific recruitment of dorsomedial striatum (DMS) and dorsolateral striatum (DLS) neurons during withdrawal. We also propose to further characterize alcohol drinking and relapse in animals that are previously made dependent by EVSA vs. animals that are made dependent by passive exposure to alcohol vapor. Finally, we propose to validate and fully characterize a novel model of extreme alcohol binging, in which animals self- administer alcohol vapor to the point of reaching blood alcohol levels of ~400 mg%, losing consciousness (“blacking out”), and exhibiting short-term memory loss. Results from these studies will provide a full characterization of alcohol drinking and relapse in animals that voluntarily develop dependence and will unveil neuronal circuits that underlie the voluntary induction and maintenance of alcohol dependence. Results from this proposal will also provide a novel animal model to study and characterize extreme alcohol binging in rodents. The proposed studies have the potential to have a sustained and powerful impact on the field of addiction because they could unveil neuronal targets that are specifically recruited during the voluntary induction of alcohol dependence and extreme binging that could be used to develop novel therapeutic approaches.

项目摘要 /摘要酒精领域的一个主要问题是缺乏自愿诱导和维护的动物模型酒精依赖。老鼠很容易自我饮酒，但饮酒量很低因此，不会产生与酒精中毒相关的血液酒精水平（100-200 mg％的％每天几个小时）。在上一个资金期间，我们成功地开发了一种新颖的自愿模型使用慢性间歇性乙醇蒸气自我诱导和维持大鼠酒精依赖性管理（EVSA）。在该模型中，动物表现出严重的成瘾行为，包括戒断，类似焦虑的行为，痛苦和响应目的地广告后果（在 EVSA 6周后，渐进式增援时间表。当前的提议寻求进一步开发此范式，确定自愿诱导酒精依赖性的神经元网络，以及描述了一种新颖的自愿模型“极端裂变”。极端酒精是一个关键的社会问题以及2017 - 2021年NIAAA战略计划的优先事项之一。暴饮暴食和极端的暴饮暴食是特别令人不安，因为它们增加了停电，酒精中毒，性侵犯，性侵犯的风险传播疾病，学习成绩不佳和发展的疾病。通过将酒精蒸气组合起来使用最先进的大脑映射技术管理，我们将确定驱动驱动的神经元网络自愿诱导酒精依赖性后，饮酒和继电器。我们的数据表明被动和积极的酒精蒸气会产生饮酒的升级，增加了获得酒精并增加继电器的动机，但依赖的自愿诱导是特征的通过特定的背侧纹状体（DMS）和背外侧纹状体（DLS）神经元的募集。提取。我们还建议进一步表征以前是动物的饮酒和救济由EVSA与动物依赖，这些动物取决于被动暴露于酒精蒸气的依赖。最后，我们建议验证和充分表征一种新型的极端酒精味模型，其中动物自我自我给予酒精蒸气达到〜400 mg％的血液酒精水平，失去意识（“涂黑”），并表现出短期记忆丧失。这些研究的结果将提供完整的自愿发展依赖并将揭晓的动物中饮酒和救济的表征自愿诱导和维持酒精依赖性的神经元电路。结果提案还将提供一种新型的动物模型来研究和表征啮齿动物中极端的酒精味。拟议的研究有可能对成瘾领域产生持续和强大的影响因为它们可以揭示在自愿诱导酒精期间专门招募的神经元靶标可用于开发新型治疗方法的依赖性和极端裂纹。