Preclinical Assessment of Medications for Alcohol Abuse

酒精滥用药物的临床前评估

基本信息

批准号：
7322024
负责人：
Elise M Weerts
金额：
$ 38.13万
依托单位：
JOHNS HOPKINS UNIVERSITY
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：
2007-09-28 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7322024
关键词：
Abstinence Address Affect Agonist Alcohol abuse Alcohol consumption Alcohol dependence Alcoholic Beverages Alcohols Animals Antiepileptic Agents Attenuated Baclofen Behavior Behavioral Benzodiazepines Brain CNR1 gene Cannabinoids Clinical Trials Complex Consumption Cues Daily Data Development Disulfiram Dopamine Dose Drug Kinetics Drug Metabolic Detoxication Flavoring Food Glutamates Goals Heavy Drinking Human In complete remission Influentials Laboratory Animals Laboratory Study Life Link Liquid substance Literature Measures Modeling Motivation Naltrexone Neurotransmitters Numbers Opioid Peptide Oranges Outcome Papio Patients Pharmaceutical Preparations Population Pre-Clinical Model Primates Procedures Psychological reinforcement Range Reinforcement Schedule Relapse Relative (related person)Research Personnel Rewards SR141716 Schedule Self Administration Self-Administered Specificity Stimulus System Testing Treatment Efficacy United States Food and Drug Administration Work acamprosate alcohol abstinence alcohol abuse therapy alcohol craving alcohol effect alcohol reinforcement alcohol seeking behavior behavior measurement craving desire drinking drug of abuse drug reinforcement drug testing gamma-Aminobutyric Acid improved non-alcoholic nonhuman primate novel pre-clinical programs receptor reinforcer response sex topiramate

项目摘要

DESCRIPTION (provided by applicant): Alcohol is one of the most commonly abused drugs in the US, with 10% of the population affected by alcohol dependence at some point in their lives. An important new focus is the development of new medications to help alcohol dependent patients reduce their alcohol use and promote abstinence. Potential targets for new medications are the multiple neurotransmitter systems of the brain reward systems including gamma- aminobutyric acid (GABA), glutamate, dopamine, cannabinoid and opioid peptides, which appear to be involved in the reinforcing effects of alcohol. Compulsive drinking can be conceptualized as a sequence of complex behaviors that terminate in alcohol consumption. Such complex sequences of behavior can be modeled in laboratory animals using chained schedules of reinforcement. The proposed studies will utilize a procedure in which initially neutral cues (lights and tones) are presented during 3 distinct components of a chained schedule of reinforcement. Each component is associated with an operant response requirement that is correlated with a distinct cue. Fulfilling the response requirement in the second component is necessary to progress to the third and final component. The primary reinforcer (alcohol or a preferred non- alcoholic beverage; Tang) will be available for self-administration only in the final component. This procedure allows the measurement of behaviors associated with alcohol anticipation, seeking, consumption and reinforcement within the same experimental session. The current proposal will evaluate the efficacy of newly proposed alcohol medications (e.g., topiramate, baclofen, 3-PBC and SR141716) in reducing alcohol seeking and consumption. In addition, current FDA-approved medications (naltrexone and acamprosate) will also be evaluated for comparison. The following hypotheses will be tested: 1) Test drugs will decrease alcohol self-administration behaviors and the amount of alcohol consumed, 2) Test drugs will decrease the motivation to gain access to alcohol, as measured by delaying onset of drinking and by reducing the maximum amount of work the subject will engage in to gain access to alcohol, 3) Decreases in self- administration and consumption produced by the test drugs will be greater for alcohol than for Tang, and 4) Test drugs will decrease the motivation to gain access to alcohol more than for Tang. These studies will provide important, previously unavailable, information on the differential behavioral efficacy of compounds that target receptor mechanisms believed to be influential in maintaining alcohol drinking and alcohol- seeking behaviors that are relevant to compulsive alcohol use and relapse in humans.

描述（由申请人提供）：酒精是美国最常见的药物之一，其中10％的人口在其生活中的某个时候受酒精依赖的影响。一个重要的新重点是开发新药物，以帮助依赖酒精的患者减少饮酒并促进戒酒。新药物的潜在靶标是大脑奖励系统的多个神经递质系统，包括γ-氨基丁酸（GABA），谷氨酸，多巴胺，大麻素，大麻素和阿片类肽，这些系统似乎参与了酒精的增强作用。强迫性饮酒可以被概念化为一系列复杂行为，这些行为终止于饮酒。这种复杂的行为序列可以在实验室动物中使用链式的加固时间进行建模。拟议的研究将利用一种程序，其中最初在锁定加固时间表的3个不同组成部分中提出了最初中性线索（灯光和音调）。每个组件与与不同的提示相关的操作响应要求相关联。在第二个组件中满足响应要求是必要的，以发展到第三个和最终组件。仅在最终组成部分中，仅可用于自我管理。该程序允许在同一实验会议中测量与酒精预期，寻求，消费和增强相关的行为。当前的提案将评估新提出的酒精药物（例如托吡酯，巴氯芬，3-PBC和SR141716）在减少饮酒和消费方面的疗效。此外，还将评估当前的FDA批准药物（Naltrexone和acamprosate）以进行比较。将测试以下假设：1）测试药物将减少酒精自我给药行为和消耗的酒精量，2）测试药物将减少降低获得酒精饮酒的动机，因为通过延迟饮酒和延迟饮酒的延迟开始，通过减少受试者的测试和消费量会降低与酒精相比的测试，3）降低药物的测试，3）的范围是3）将减少获得酒精饮酒的动力，而不是唐。这些研究将提供有关化合物的差异行为疗效的重要，以前无法使用的信息，这些信息靶向被认为对维持与强迫性饮酒和人类复发有关的饮酒和寻求酒精饮酒行为具有影响力的受体机制。