The Effect of Sleep Deprivation on Conditioned Place Preference to Cocaine.

 描述（由申请人提供）： 药物滥用和睡眠障碍是美国和世界各地的共同问题。仅在美国，就有超过2000万人患有药物滥用和/或睡眠障碍。与一般美国人口类似，睡眠障碍和物质使用在退伍军人中很常见（国家药物管制政策办公室通讯，2010年），其中患有创伤后应激障碍（PTSD）的人群表现出特别高的比率。此外，睡眠障碍/困难通常与药物滥用共病（Shibley等人，2008; Gromov和Gromov，2009）。睡眠障碍已经在活跃药物使用期间、戒断期间和禁欲期间得到证实（Morgan等人，2006; Morgan等人，2008年）。有大量证据表明，人类的睡眠中断是复发的可靠预测因子（Brower等人，（2001）失眠 经常被引用为物质使用的原因（Brower等人，2001年）。然而，很少有人试图直接评估睡眠不足是否在未来的药物使用中起因果作用。一个基本的、至今尚未得到解答的问题是，睡眠不足是否会增加药物的食欲.在目前的提议中，睡眠剥夺增强可卡因的奖励特性的假设将使用条件位置偏好（CPP）任务进行测试。CPP任务评估线索诱导的药物寻求条件试验后，假定的食欲（可卡因）和假定的中性（盐水）刺激。在可卡因条件试验之前或在探针试验之前，小鼠将经历短时间的睡眠剥夺，以测试是否 睡眠剥夺分别改变可卡因条件性位置偏好的获得或表达。初步证据表明，睡眠不足确实会增加对可卡因配对环境的偏好。最后，两个神经调质系统，腺苷和食欲素，将被探讨作为可能的机制，睡眠，或其损失，可能会影响奖励行为。这两个系统以前都涉及睡眠/清醒活动和成瘾。行为学、遗传学和药理学技术将用于进行拟议的实验。项目导师提供与研究项目相关的所有领域的专业知识，包括睡眠/清醒行为（格林，柳泽），成瘾研究（自我），腺苷（格林）和食欲素（柳泽）系统。

 DESCRIPTION (provided by applicant): Project summary: Substance abuse and sleep disorders are both common problems in the United States and around the world. In the US alone, over 20 million people suffer from substance abuse and/or sleep disorders. Similar to the general US population, sleep disorders and substance use are common in veterans (Newsletter of the National Office of Drug Control Policy, 2010), with populations such as those with post-traumatic stress disorder (PTSD) exhibiting especially high rates. Furthermore, sleep disorders/difficulties are often co-morbid with substance abuse (Shibley et al., 2008; Gromov and Gromov, 2009). Sleep disturbances have been demonstrated during active drug use, during withdrawal, and during abstinence periods (Morgan et al., 2006; Morgan et al., 2008). There is abundant evidence that sleep disruption in humans is a robust predictor of relapse (Brower et al., 2001) and difficulty sleeping is often cited as a reason for substance use (Brower et al., 2001). However, there have been few attempts to directly assess whether sleep loss has a causal role in future drug use. One basic, and as of yet unanswered, question is whether sleep loss augments the appetitive value a drug. In the current proposal, the hypothesis that sleep deprivation enhances the rewarding properties of cocaine will be tested using the conditioned place preference (CPP) task. The CPP task assesses cue-induced drug seeking following conditioning trials to a presumed appetitive (cocaine) and a presumed neutral (saline) stimulus. Mice will undergo short periods of sleep deprivation either prior to cocaine conditioning trials or prior to the probe trial to test whether sleep deprivation alters cocaine conditioned place preference acquisition or expression, respectively. Preliminary evidence suggests that sleep deprivation does increase preference for the cocaine-paired context. Finally, two neuromodulator systems, adenosine and orexin, will be probed as possible mechanisms by which sleep, or loss thereof, could impact reward behavior. These two systems have previously been implicated in both sleep/waking activity and addiction. Behavioral, genetic, and pharmacological techniques will be used to carry out the proposed experiments. The project mentors provide expertise in all the fields relevant to the research project, including sleep/waking behavior (Greene, Yanagisawa), addiction research (Self), and the adenosine (Greene) and orexin (Yanagisawa) systems.