Target Validation Core Rats

描述（由申请人提供）：本申请提出了一个核心组成的INIA-West联盟的任务是确定目标药物治疗酗酒。代理人将根据从INIA-West内的项目获得的信息确定。 将使用已建立的大鼠行为方法，以系统的方式检查药物，以确定它们是否改变反映酒精中毒各个方面的行为，包括酗酒、负面影响和先入为主的预期。试验以有序的方式进行，明确规定了继续或停止药物研究的决策点。代理人的能力，改变行为的指示酗酒检查使用的操作性自我管理的酒精累进比例的时间表和有希望的结果，然后由位置条件反射和2瓶偏好程序的维护。负性情绪的减轻通过用高架十字迷宫和强迫游泳测试测量戒断症状和焦虑和抑郁样行为来评估。 先占-预期（“渴望”）通过药物/线索诱导的已熄灭的操作性反应的恢复、条件接近和信号跟踪来评估。鉴于预防复发在酒精中毒治疗中的重要性，这一组“渴望”研究是赠款的重点，也是使用大鼠的原因，因为这些程序更难以用小鼠建立。此外，由于过量的酒精会导致认知缺陷，这可能会干扰心理治疗（通常与药物治疗相结合），我们还将使用标准的学习和记忆任务（例如，恐惧条件反射、物体识别、延迟交替）。 研究将在长期暴露于酒精蒸汽的大鼠中进行。该项目与罗伯茨和贝尔项目密切互动，以确认或扩展调查结果，从而提高对所获得结果的信心。最后，与其他项目和核心合作，并使用分子遗传学和神经药理学方法，我们将确认目标药物的神经生物学作用，以改变慢性酒精效应。

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.