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

睡眠剥夺对可卡因条件性场所偏好的影响。

• 批准号: 9086107
• 负责人: Theresa Eileen Bjorness
• 金额: --
• 依托单位: VA NORTH TEXAS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9086107
• 关键词: 2-tyrosine; Abstinence; Adenosine; Adenosine A1 Receptor; Afghanistan; Alcohol or Other Drugs use; Alcohols; American; Animals; Attenuated; Behavior; Behavioral Genetics; Cocaine; Control Groups; Corticosterone; Cues; Diagnosis; Disease; Dose; Drug Controls; Drug usage; Exhibits; Freedom; Future; Gambling; General Population; Human; Hypothalamic structure; Illicit Drugs; Image; Iraq; Knock-out; Knockout Mice; Label; Lateral; Measures; Mentors; Morphine; Mus; National Institute of Drug Abuse; National Institute of Neurological Disorders and Stroke; Neuromodulator; Neurons; Newsletter; Pharmaceutical Preparations; Policies; Population; Post-Traumatic Stress Disorders; Property; Receptor Activation; Relapse; Reporting; Research; Research Project Grants; Rewards; Role; Saline; Sleep; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Sleeplessness; Staining method; Stains; Stimulus; Stress; Substance abuse problem; System; Techniques; Testing; Tyrosine 3-Monooxygenase; United States; Ventral Tegmental Area; Veterans; War; Withdrawal; addiction; conditioning; coping; deprivation; economic cost; hypocretin; operation; preference; public health relevance; receptor; research study; response; restraint; sleep regulation

 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.

 描述（由申请人提供）： 项目摘要：药物滥用和睡眠障碍是美国和世界各地的常见问题。仅在美国，就有超过 2000 万人患有药物滥用和/或睡眠障碍。与美国普通人群类似，睡眠障碍和药物滥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），而患有创伤后应激障碍 (PTSD) 等人群的发病率尤其高。此外，睡眠障碍/困难常常与药物滥用同时发生（Shibley 等人，2008 年；Gromov 和 Gromov，2009 年）。在主动吸毒、戒断和禁欲期间，睡眠障碍已被证实（Morgan 等，2006 年；Morgan 等，2008 年）。有大量证据表明，人类睡眠中断是旧病复发和睡眠困难的有力预测因素（Brower 等，2001） 经常被引用为物质使用的原因（Brower 等，2001）。然而，很少有人尝试直接评估睡眠不足是否与未来的药物使用有因果关系。一个基本且尚未得到解答的问题是，睡眠不足是否会增加药物的食欲。在当前的提案中，睡眠剥夺会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 任务评估在假定的食欲（可卡因）和假定的中性（盐水）刺激的条件试验后线索诱导的药物寻求。在可卡因调节试验之前或在探索试验之前，小鼠将经历短暂的睡眠剥夺，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人们对可卡因配对的偏好。最后，将探讨两种神经调节系统，腺苷和食欲素，作为睡眠或睡眠缺失影响奖赏行为的可能机制。这两个系统之前曾被认为与睡眠/清醒活动和成瘾有关。行为、遗传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（Greene、Yanagisawa）、成瘾研究（Self）以及腺苷（Greene）和食欲素（Yanagisawa）系统。