PREOPTIC AREA AND PHARMACOLOGIC SLEEP INDUCTION

描述（改编自申请人摘要）：尽管大约有20 每年有100万张催眠药物的处方， 它们起作用的分子机制，以及 他们所做的。 仍然不清楚。 这一问题因广泛的 一系列药理学类别的化合物，诱导睡眠，它是 不确定这些不同的代理是否在其机制或网站的不同， 行动上 调查员已经开始着手调查一个案子 几种类型的睡眠诱导化合物的机制可能涉及 与苯二氮卓（BZ）-GABA a受体复合物的相互作用。 的 目前的建议，根据调查员的意见， 在内侧核微量注射戊巴比妥或BZ催眠药三唑仑 下丘脑前部的视前区（MPA）诱导睡眠。 地址 睡眠诱导药物作用的解剖学部位。 目标是 将研究者实验室的这些观察结果汇总在一起， 来自其他实验室的结果表明， 微量注射乙醇和腺苷 研究者应探索 这些意见还涉及以下问题： 1. 当所有这些化合物都在同一个实验室中检测时， 实验室，在类似的条件下，这些不同的代理人显示明确的 剂量反应性？ 2. 这些效应是否特异于BZ-GABA a识别位点？ 3. 这些影响是MPA特有的，还是注射后会发生 到其他结构？ 4. 它们是由于改变下丘脑温度的结果，还是 通过更直接的机制？ 5. 在以下情况下，这些药物诱导睡眠是否需要完整的MPA？ 给药后 从更广泛的意义上说，这项建议的目标是超越 简单鉴定催眠化合物的常规方法，以及 而是提出一系列关键问题， 关于任何改变睡眠的物质，包括：1）它在哪里起作用？ 2)它作用于哪些受体？3)生理过程 它相互作用吗？以及4）哪些大脑部位是催眠的关键 效果？ 因此，研究者的目标是既要描述 四类催眠物质的性质，并开始建立一个 框架，使目前多样和复杂的文献， 睡眠物质更加结构化和可理解。

DESCRIPTION (Adapted from applicant's abstract): Although approximately 20 million prescriptions for hypnotic medications are written each year, the molecular mechanisms by which they act, and the neuroanatomic site(s) at which they act. remain unclear. This problem is complicated by the wide range of pharmacologic classes of compounds which induce sleep, and it is uncertain whether these various agents differ in their mechanisms or site of action. The investigator has begun to build a case that a common molecular mechanism for several types of sleep-inducing compounds may involve interaction with the benzodiazepine (BZ)-GABAa receptor complex. The current proposal, based on the investigator's observations that microinjection of pentobarbital or the BZ hypnotic triazolam into the medial preoptic area (MPA) of the anterior hypothalamus induces sleep. addresses the anatomical site(s) of action of sleep-inducing drugs. The goal is to bring together these observations from the investigator's laboratory and those from other laboratories indicating similar effects from microinjections of ethanol and adenosine. The investigator shall explore these observations further, addressing the following questions: 1. Do these findings hold when all these compounds are examined in the same laboratory, under similar conditions, and do these various agents show clear dose-responsiveness? 2. Are these effects specific to the BZ-GABAa recognition site? 3. Are these effects specific to the MPA, or do they occur with injection into other structures? 4. Do they result as a consequence of altering hypothalamic temperature, or by a more direct mechanism? 5. Is an intact MPA necessary for sleep induction by these agents when given parenterally? In a broader sense, the goal of this proposal it to move beyond the conventional approach of simply identifying a hypnogenic compound, and instead to develop a series of critical questions which should be asked about any substance which alters sleep, including: 1) where does it act?; 2) on which receptors does it act?; 3) with which physiological processes does it interact?; and 4) which brain sites are critical for its hypnogenic effect? The investigator's goal, then, is both to characterize the properties of four classes of hypnogenic substances, and to begin to build a framework to make the currently diverse and complex literature on putative sleep substances more structured and comprehensible.