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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