Department of Psychiatry, UTSW and Dallas VAMC, Dallas, TX, USA.
Curr Neuropharmacol. 2009 Sep;7(3):238-45. doi: 10.2174/157015909789152182.
Over the last several decades the idea that adenosine (Ado) plays a role in sleep control was postulated due in large part to pharmacological studies that showed the ability of Ado agonists to induce sleep and Ado antagonists to decrease sleep. A second wave of research involving in vitro cellular analytic approaches and subsequently, the use of neurochemical tools such as microdialysis, identified a population of cells within the brainstem and basal forebrain arousal centers, with activity that is both tightly coupled to thalamocortical activation and under tonic inhibitory control by Ado. Most recently, genetic tools have been used to show that Ado receptors regulate a key aspect of sleep, the slow wave activity expressed during slow wave sleep. This review will briefly introduce some of the phenomenology of sleep and then summarize the effect of Ado levels on sleep, the effect of sleep on Ado levels, and recent experiments using mutant mouse models to characterize the role for Ado in sleep control and end with a discussion of which Ado receptors are involved in such control. When taken together, these various experiments suggest that while Ado does play a role in sleep control, it is a specific role with specific functional implications and it is one of many neurotransmitters and neuromodulators affecting the complex behavior of sleep. Finally, since the majority of adenosine-related experiments in the sleep field have focused on SWS, this review will focus largely on SWS; however, the role of adenosine in REM sleep behavior will be addressed.
在过去的几十年里，由于药理学研究表明腺苷（Ado）激动剂能够诱导睡眠，而 Ado 拮抗剂能够减少睡眠，因此提出了腺苷在睡眠控制中起作用的观点。第二波研究涉及体外细胞分析方法，随后使用神经化学工具，如微透析，鉴定了脑桥和基底前脑觉醒中心内的一群细胞，其活动与丘脑皮质激活紧密相关，并受到 Ado 的紧张性抑制控制。最近，遗传工具被用于表明 Ado 受体调节睡眠的一个关键方面，即慢波睡眠期间表达的慢波活动。这篇综述将简要介绍睡眠的一些现象学，然后总结 Ado 水平对睡眠的影响、睡眠对 Ado 水平的影响，以及最近使用突变小鼠模型来描述 Ado 在睡眠控制中的作用的实验，并以讨论哪些 Ado 受体参与这种控制结束。总的来说，这些实验表明，虽然 Ado 在睡眠控制中确实起作用，但它是一种具有特定功能意义的特定作用，它是影响睡眠这种复杂行为的许多神经递质和神经调质之一。最后，由于睡眠领域的大多数与腺苷相关的实验都集中在 SWS 上，因此本综述将主要集中在 SWS 上；然而，腺苷在 REM 睡眠行为中的作用也将被提及。
