Target Validation Core Rats

目标验证核心大鼠

• 批准号: 8228566
• 负责人: Therese A Kosten
• 金额: $ 21.69万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-27 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8228566
• 关键词: Abstinence; Address; Affect; Alcohol consumption; Alcohol dependence; Alcohol withdrawal syndrome; Alcoholism; Alcohols; Animal Model; Anxiety; Appetitive Behavior; Attenuated; Behavior; Behavioral; Behavioral Assay; Chronic; Cognitive; Cognitive deficits; Collaborations; Consummatory Behavior; Cues; Disease; Elements; Genes; Goals; Grant; Intoxication; Learning; Maintenance; Measures; Memory; Mental Depression; Methods; Modeling; Molecular; Molecular Genetics; Mus; Negative Reinforcements; Neurobiology; New Agents; Pharmaceutical Preparations; Pharmacological Treatment; Phase; Positive Reinforcements; Procedures; Process; Rattus; Relapse; Research; Schedule; Self Administration; Swimming; System; Testing; Validation; Withdrawal; addiction; alcohol effect; alcohol exposure; alcohol use initiation; alcoholism pharmacotherapy; alcoholism therapy; base; behavior test; classical conditioning; cognitive function; conditioned fear; conditioning; craving; depressive symptoms; disorder later incidence prevention; drinking; follow-up; innovation; novel; object recognition; preference; problem drinker; programs; psychologic; skills; trait; translational approach; vapor

DESCRIPTION (provided by applicant): This application proposes a core integral to the INIA-West Consortium tasked to identify target medications to treat alcoholism. Agents will be identified based on information obtained from projects within INIA-West. The agents will be examined to determine if they alter behaviors reflective of the various aspects of alcoholism including binge-intoxication, negative affect, and preoccupation-anticipation in a systematic manner using established behavioral methods with rats. Tests are conducted in an orderly manner with clearly defined decision points for continuation or cessation of studies with an agent. An agent's ability to alter behaviors indicative of binge-intoxication is examined using maintenance of operant self-administration of alcohol under progressive ratio schedules and promising results followed by place conditioning and 2-bottle preference procedures. Alleviation of negative affect is assessed by measuring withdrawal signs and anxiety- and depressive-like behaviors with elevated plus maze and forced swim tests. Preoccupation-anticipation ("craving") is assessed with drug/cue-induced reinstatement of extinguished operant responding, conditioned approach, and sign-tracking. This set of "craving" studies is a focal point of the grant given the importance of relapse prevention in alcoholism treatment and a reason rats are used as these procedures are more difficult to establish with mice. Further, because excessive alcohol can cause cognitive deficits that would likely interfere with psychological treatments (which are often combined with pharmacological treatments), we will also assess whether target agents alter cognitive function using standard learning and memory tasks (e.g., fear conditioning, object recognition, delayed alternation). Studies will be conducted in rats that have been chronically exposed to alcohol vapors. This project interacts closely with the Roberts and Bell projects to confirm or extend findings allowing greater confidence in results obtained. Finally, in collaboration with other projects and cores and using molecular genetic and neuropharmacological approaches, we will confirm the neurobiological effects of the target agents to alter chronic alcohol effects. PUBLIC HEALTH RELEVANCE: The goal of this research program is to establish a behavioral testing core for the INIA-West Consortium aimed at testing potential pharmacotherapeutic agents for alcoholism. The main focus of this core is to conduct tests reflective of "craving" although other aspects of alcoholism (intoxication, negative affect) will be addressed and results compared to those of the Bell and Roberts cores.

描述（由申请人提供）：本申请提出了旨在识别目标药物治疗酒精中毒的INIA-West Consortium不可或缺的核心组成部分。将根据从Inia-West内的项目获得的信息来识别代理。 将检查代理人，以确定它们是否改变了酒精中毒的各个方面的行为，包括暴饮暴食，负面影响和使用既定的行为方法与大鼠进行系统的方式进行系统的观察。测试以有序的方式进行，并具有明确定义的决策点，以延续或停止与代理商进行研究。通过维持在渐进式比率计划下酒精的操作者自我管理以及有希望的结果，随后是位置调节和2瓶偏好程序，可以检查代理改变行为表明暴饮暴及的行为的能力。通过测量戒断迹象以及焦虑和抑郁样行为来评估负面影响的缓解，并以较高的迷宫和强迫游泳测试来评估。 通过药物/提示引起的恢复原始响应，条件方法和标志跟踪的恢复原状的恢复原状，对全体期望（“渴望”）进行了评估。鉴于在酒精中毒治疗中预防复发的重要性，这组“渴望”研究是赠款的一个焦点，并且由于这些程序更难用小鼠建立，因此使用了大鼠的原因。此外，由于过量的酒精会导致认知缺陷可能会干扰心理治疗（通常与药理治疗结合使用），因此我们还将评估目标药物是否使用标准学习和记忆任务（例如，恐惧条件，对象识别，延迟交替）来改变认知功能）。 将在长期暴露于酒精蒸气的大鼠中进行研究。该项目与罗伯茨和贝尔项目紧密互动，以确认或扩展发现，从而使获得的结果更有信心。最后，与其他项目和核心合作，并使用分子遗传和神经药物方法，我们将确认目标药物的神经生物学作用改变慢性酒精效应。 公共卫生相关性：该研究计划的目标是为INIA-West联盟建立一个行为测试核心，旨在测试潜在的酒精中毒药物治疗剂。该核心的主要重点是进行反映“渴望”的测试，尽管将解决酒精中毒（中毒，负面影响）的其他方面，并与贝尔和罗伯茨核心的结果相比。