Mouse Target Assessment Core

鼠标目标评估核心

基本信息

批准号：
8516914
负责人：
AMANDA J ROBERTS
金额：
$ 29.25万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-05 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8516914
关键词：
Alcohol abuse Alcohol consumption Alcohol dependence Alcoholism Alcohols Amygdaloid structure Animal Model Behavioral Brain region Chronic Circadian Rhythms Data Dependence Disulfiram Equipment Ethanol Exposure to FDA approved Funding Funding Opportunities Genes Genetically Engineered Mouse Goals Heavy Drinking Injury Intake Investigation Lead Letters Mental disorders Modeling Molecular Mus Naltrexone National Institute on Alcohol Abuse and Alcoholism Neuronal Plasticity Neurosciences Pathway interactions Pattern Pharmaceutical Preparations Pharmacotherapy Phenotype Physiological Play Public Health Publishing RNA Interference Rattus Relapse Research Research Personnel Risk Role Services Social Problems System Technology Testing Time Tissues Work acamprosate alcohol craving alcohol effect alcohol exposure alcoholism therapy animal model development base binge drinking chromatin modification combat craving drinking genetic analysis improved in vivo mouse model neuroinflammation novel peptide hormone psychologic research study therapeutic target therapy development vapor

项目摘要

DESCRIPTION (provided by applicant): Heavy alcohol drinking and binge drinking are patterns of alcohol consumption considered abusive and which are associated with increased risk of injuries, physical maladies, mental illness, and increased risk of dependence upon alcohol. Once dependent, alcohol abuse becomes chronic; with strong craving, continued use despite physical, psychological and social problems, and loss of control over intake. Excessive drinking is a hallmark of both abuse and dependence. INIA-West has focused on excessive alcohol drinking as a target for animal model development, cellular and molecular investigation, and, ultimately, on medications target identification. While there are currently three FDA approved medications for alcohol dependence available, disulfiram, naltrexone, and acamprosate, there is still a push by NIAAA to identify more efficacious pharmacotherapies to combat the deleterious effects of heavy alcohol consumption and alleviate those effects that lead to continued intake and relapse. The overarching theme of the Mouse Target Assessment Core is to use INIA models of excessive alcohol drinking and the behavioral effects of alcohol to explore targets that have been identified over the past funding periods. The specific goals of the Mouse Target Assessment Core (MTAC) are to: 1) Continue to optimize and extend INIA models of excessive drinking and provide test services and tissues to consortium investigators; 2) Identify and test new target compounds based on INIA-West-generated data; 2) Improve in vivo testing of potential pharmacotherapeutic targets; 3) Work closely with the Rat Target Assessment Core (Kosten) and the Rat Animal Models and Gene Testing Core (Bell) to standardize our target identification in a cross-species manner; 4) Work with INIA investigators as targets are identified and with the Steering Committee and Scientific Advisory Board to prioritize them for testing and determine which to pursue further; and 5) Use RNA interference (RNAi) technology and genetically engineered mice to examine target systems for which usable compounds are, as yet, unavailable as well as to confirm and extend positive results.

描述（由申请人提供）：大量饮酒和暴饮被视为滥用酒精消费模式，与受伤、身体疾病、精神疾病的风险增加以及对酒精依赖的风险增加相关。一旦产生依赖，酗酒就会变成慢性；具有强烈的渴望，尽管存在身体、心理和社会问题，但仍继续使用，并且对摄入量失去控制。过量饮酒是虐待和依赖的标志。 INIA-West 专注于将过量饮酒作为动物模型开发、细胞和分子研究的目标，并最终确定药物目标。虽然目前 FDA 批准了三种治疗酒精依赖的药物：双硫仑、纳曲酮和阿坎酸，但 NIAAA 仍在努力寻找更有效的药物疗法，以对抗大量饮酒的有害影响，并减轻导致持续饮酒的影响并复发。小鼠目标评估核心的首要主题是使用过量饮酒的 INIA 模型和酒精的行为影响来探索过去资助期间确定的目标。小鼠目标评估核心（MTAC）的具体目标是： 1）继续优化和扩展过度饮酒的 INIA 模型，并向联盟研究人员提供测试服务和组织； 2) 根据 INIA-West 生成的数据识别和测试新的目标化合物； 2）改进潜在药物治疗靶点的体内测试； 3）与大鼠目标评估核心（Kosten）和大鼠动物模型和基因测试核心（Bell）密切合作，以跨物种的方式标准化我们的目标识别； 4) 与 INIA 研究人员合作确定目标，并与指导委员会和科学咨询委员会合作确定测试的优先顺序并确定进一步追求的目标； 5) 使用RNA干扰（RNAi）技术和基因工程小鼠来检查尚未获得可用化合物的目标系统，并确认和扩展积极结果。