DRUG ABUSE, SLEEP AND COGNITION

只有当神经调质水平、睡眠和认知水平的变化之间的联系得到很好的描述和分析时，药物滥用的许多功能障碍方面才能被理解和有效治疗。 该提案集中于两类药物的认知效应，即精神兴奋剂（此处为可卡因）和选择性5-羟色胺再摄取抑制剂（此处为帕罗西汀），已知这两种药物都能增强大脑的单胺能神经元系统。 利用我们的基本神经生物学知识以及睡眠和认知理论，我们对介导可卡因滥用认知效应的睡眠和神经调节因素进行了具体预测。我们将联合收割机与我们经过验证的流动睡眠监测仪Nightcap相结合，认知测试可以在分析睡眠测量的同一台Macintosh计算机上进行。 通过应用这种综合的门诊系统，药物对睡眠和认知的影响的研究将变得更加经济和自然。 我们计划在两个独特的研究机构，即哥伦比亚医学院物质使用研究中心的可卡因自我管理实验室和哈佛神经生理学睡眠实验室使用这种动态监测能力，以研究睡眠、单胺能机制及其相互作用如何介导可卡因滥用的认知后遗症。这一建议的核心是这样一种想法，即滥用的单胺能药物如可卡因，首先增强但随后损害觉醒-睡眠周期的神经调节动力学，最终对认知功能产生有害影响。 我们提出了一系列的研究，这是理论驱动的，并测试特定的假设，这将使我们能够隔离和描述的睡眠和单胺能神经调节剂对可卡因的使用和禁欲的已知的负面认知影响的相互关联的影响。在一组七个补充协议，我们将比较单独和联合的影响，对睡眠和认知性能的重复可卡因管理和禁欲，管理和停止帕罗西汀，REM睡眠剥夺。 这项拟议中的研究将回答有关睡眠的认知益处以及当药物滥用时这些益处如何丧失的基本问题。

Many dysfunctional aspects of drug abuse can be understood and effectively treated only when the links between changes in levels of neuromodulators, sleep, and cognition are well described and analyzed. This proposal focuses on the cognitive effects of two drug classes, the psychostimulants (here cocaine) and the selective serotonin reuptake inhibitors or SSRIs (here paroxetine), both of which are known to potentiate the monoaminergic neuronal systems of the brain. Drawing upon our basic neurobiological knowledge and theories of sleep and cognition, we have generated specific predictions on the sleep and neuromodulatory factors mediating the cognitive effects of cocaine abuse. We will combine our validated ambulatory sleep monitor, the Nightcap, with cognitive tests that can be presented and performed on the same Macintosh computer that analyzes sleep measurements. The study of drug effects on sleep and cognition will be made considerably more economical and naturalistic by the application of this integrated ambulatory system. We plan to use this ambulatory monitoring capability at two unique research facilities, the cocaine self-administration laboratory of the Substance Use Research Center at Columbia Medical School and the Harvard Laboratory of Neurophysiology sleep laboratory, to study how sleep, monoaminergic mechanisms, and their interactions may mediate the cognitive sequelae of cocaine abuse. At the heart of this proposal is the idea that the monoaminergic drugs of abuse such as cocaine, first potentiate but then later impair the neuromodulatory dynamics of the wake-sleep cycle with ultimately deleterious effects upon cognitive functioning. We propose a series of studies which are theory-driven and which test specific hypotheses that will allow us to isolate and describe the interrelated effects of sleep and monoaminergic neuromodulators on the known negative cognitive effects of cocaine use and abstinence. In a set of seven complementary protocols, we will compare the individual and combined effects on sleep and cognitive performance of repeated cocaine administration and abstinence, administration and discontinuation of paroxetine, and REM sleep deprivation. The proposed research will answer fundamental questions regarding the cognitive benefits of sleep and how these benefits are lost when drugs are abused.