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PREOPTIC AREA AND PHARMACOLOGIC SLEEP INDUCTION

视前区和药理学睡眠诱导

基本信息

批准号：
6362823
负责人：
Paul R Vezina
金额：
$ 23.5万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-04-01 至 2004-02-29
项目状态：
已结题

项目摘要

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.

描述(改编自申请人的摘要)：虽然大约有20个每年有数百万张催眠药处方被开出，它们作用的分子机制和神经解剖部位(S) 他们采取的行动。目前仍不清楚。这个问题由于范围广泛而变得复杂起来一系列能诱导睡眠的化合物的药理类别，它是不确定这些不同的毒剂是否在它们的机制或部位上不同行动。研究人员已经开始建立一个案例，证明一种常见的分子几种类型的催眠化合物的作用机制可能包括与苯二氮(BZ)-GABAA受体复合体的相互作用。这个目前的提案，根据调查人员的观察，戊巴比妥或BZ催眠剂三唑仑内侧微量注射下丘脑前部的视前区是睡眠的诱导区。地址安眠药作用的解剖部位(S)。我们的目标是将这些来自调查员实验室的观察结果汇总在一起来自其他实验室的研究表明，来自微量注射乙醇和腺苷。调查员将探索这些意见进一步回答了以下问题： 1.当所有这些化合物都在同一组中被检查时，这些发现是否成立实验室，在相似的条件下，这些各种试剂是否显示出明显的剂量反应？ 2.这些影响是否仅限于BZ-GABAA识别位点？ 3.这些影响是特定于MPA的，还是发生在注射过程中到其他建筑里吗？ 4.它们是下丘脑温度变化的结果，还是通过一种更直接的机制？ 5.当这些药物在以下情况下诱导睡眠时，是否需要完整的MPA 非肠道给药？从更广泛的意义上讲，这项提议的目标是超越简单地识别催眠化合物的传统方法，以及而是开发一系列关键问题，这些问题应该被问到关于任何改变睡眠的物质，包括：1)它在哪里起作用？ 2)作用于哪些受体；3)作用于哪些生理过程它有相互作用吗？以及4)哪些大脑部位对其催眠至关重要效果如何？因此，调查人员的目标是既要确定四类催眠物质的性质，并开始构建一种框架，使目前多样化和复杂的关于推定的文献睡眠物质更有条理，更容易理解。