Reducing alcohol-seeking behavior in a rat model of alcohol dependence

项目总结/摘要 过度饮酒是由各种因素驱动的，这些因素是生物的，心理的和社会的。 这些因素如何导致问题性饮酒，然后在恢复后复发的程度差异很大 在个人层面上。一个共同的因素呈现给所有的用户的酒精是一套线索密切相关 酒精消费。可靠地先于酒精可用性的环境线索和随后的 消费可以获得引发条件反应的能力，如酒精寻求行为，并促进 酗酒问题 目前对酒精使用障碍的治疗包括线索暴露疗法，这是一种行为程序， 在没有酒精的情况下，哪些酒精提示系统地呈现，以促进减少或“消除” 线索条件反应的能力。不幸的是，灭绝很少是永久性的： 酗酒的反应很容易复发我们最近表明，对标准的修改 消光过程（即，线索诱导的记忆提取阶段）阻止了酒精的回归- 具有中等酒精消耗水平的大鼠的寻找行为（Alfreesi等，2017年）。这 “提取+消除”方法具有巨大的潜力，因为对线索暴露疗法进行简单的修改 用于酒精康复的方案可以显着提高预防复发的几率， 治疗 因此，将我们的初步发现扩展到酒精依赖的大鼠模型是至关重要的， 人类酗酒的状况事实上，没有任何研究系统地研究了 消退，更不用说检索+消退，在酒精依赖的大鼠模型中。因此，我们将确定 影响依赖性大鼠酒精寻求行为消退和复发的参数，以及进一步 检查是否检索+灭绝是同样有效地防止复发依赖大鼠，因为它是在非- 依赖的老鼠然后，我们将探讨大脑中寻求酒精行为消退的神经基质。 依赖大鼠和测试假设，检索+灭绝从事神经机制，是不同的 标准灭绝。

PROJECT SUMMARY/ABSTRACT Excessive alcohol use is driven by various factors that are biological, psychological, and social in nature. The degree of how these factors contribute to problematic drinking and then relapse after recovery vary widely at the individual level. One common factor presented to all the users of alcohol is the set of cues closely linked to alcohol consumption. Environmental cues that reliably precede alcohol availability and subsequent consumption can gain the ability to elicit conditioned responses such as alcohol-seeking behavior and promote problematic drinking. Current treatment for alcohol use disorder includes cue-exposure therapy, a behavioral procedure in which alcohol cues are systematically presented in the absence of alcohol to promote a reduction or “extinction” of cue-conditioned responses. Unfortunately, extinction is rarely permanent: extinguished cue-conditioned alcohol-seeking responses are highly susceptible to relapse. We recently showed that a modification to standard extinction procedure (i.e., cue-induced memory retrieval session prior to extinction) blocked the return of alcohol- seeking behavior of rats with moderate level of alcohol consumption (Cofresi et al., 2017). This “retrieval+extinction” approach has enormous potential in that a simple modification to cue-exposure therapy protocols used in alcohol rehabilitation could significantly improve the odds of preventing relapse following treatment. It is thus crucial to extend our initial finding to a rat model of alcohol dependence that better mimics the human conditions of alcohol abuse. In fact, no study has systematically examined the nature and mechanism of extinction, let alone retrieval+extinction, in a rat model of alcohol dependence. Therefore, we will determine parameters that influence extinction and relapse of alcohol-seeking behavior in dependent rats, and further examine whether retrieval+extinction is equally effective at preventing relapse in dependent rats as it was in non- dependent rats. Then, we will probe the neural substrates underlying extinction of alcohol-seeking behavior in dependent rats and test the hypothesis that retrieval+extinction engages neural mechanisms that are distinct from standard extinction.