RECEPTORS IN THE CENTRAL NERVOUS SYSTEM--BIOCHEMISTRY TO BEHAVIOR

目前认为，苯二氮卓类药物与 特异性神经元膜受体启动一系列神经元事件 导致GABA介导的氯渗透性增强。 的 后者的主要药理作用的行为结果 苯二氮卓类，即其抗焦虑药、抗惊厥药、催眠药， 肌肉松弛作用。 除了苯二氮卓类药物， 轻微镇静剂类的镇静/催眠剂（例如 巴比妥酸盐）似乎与一个或多个组分的相互作用， 苯二氮卓/GABA受体复合物，因此后者已被提出 作为一种常见的轻微镇静剂作用的部位。 的诸多方面都 目前正在研究苯二氮卓类/GABA受体复合物，包括 受体的纯化， 识别激动剂、拮抗剂或反向剂受体复合物 激动剂 最近的工作集中在使用体外系统， 测量亚细胞制剂中GABA受体-效应器偶联 大鼠脑（突触神经体）。 这项技术极大地促进了 巴比妥酸盐和GABA受体介导的氯离子通量的研究， 这是第一个研究GABA功能的可靠方法， 体外受体。 利用这种方法，我们研究了 受欢迎的抗焦虑/麻醉剂乙醇与GABA受体 复杂，并发现乙醇和所有短链醇测试， 能够刺激该受体，并且在低药理学相关性 浓度的 在相关的研究中，我们发现了一种新的 咪唑苯并二氮杂卓，Ro 15，45 l3，其阻断了 乙醇对GABA受体介导的36 Cl摄取以及许多 乙醇的行为影响。 在其他研究中，我们研究了 放射性标记的苯二氮卓类受体拮抗剂Ro 15 -1788， 在体内测量苯二氮卓受体。 我们的研究结果证实了 这种技术的适用性，并已证明显着的效果， 巴比妥酸盐、乙醇和“应激”对体内苯二氮卓受体的影响。

It is currently believed that the interaction of benzodiazepines with a specific neuronal membrane receptor initiates a series of neuronal events resulting in an enhancement of GABA-mediated chloride permeability. The latter results behaviorally in the major pharmacological actions of benzodiazepines, namely their anxiolytic, anticonvulsant, hypnotic, and muscle relaxant actions. In addition to benzodiazepines, a variety of sedative/hypnotic agents of the minor tranquilizer class (e.g. the barbiturates) appear to interact with one or more components of the benzodiazepine/GABA receptor complex, and thus the latter has been proposed as a common site of minor tranquilizer action. Several aspects of the benzodiazepine/GABA receptor complex are currently being studied, including purification of the receptor, characterization of multiple binding sites on the receptor complex which recognizes agonist, antagonists or inverse agonists. Recent work has focused on using an in vitro system for measuring GABA receptor-effector coupling in a subcellular preparation from rat brain (the synaptoneurosome). This technique has greatly facilitated studies on barbiturate and GABA receptor-mediated chloride flux and has resulted in the first reliable method for studying the function of the GABA receptor in vitro. Using this method we have studied the interaction of the popular anxiolytic/intoxicant ethyl alcohol with the GABA receptor complex and have found that ethanol and all short-chain alcohols tested are capable of stimulating this receptor and at low pharmacologically-relevant concentrations. In related studies we have identified a novel imidazobenzodiazepine, Ro15,45l3, which blocks both the in vitro effects of ethanol on GABA receptor-mediated 36Cl-uptake as well as many of the behavioral effects of ethanol. In other studies we have examined the use of the radiolabelled benzodiazepine receptor antagonist Ro15-1788 for measuring benzodiazepine receptors in vivo. Our results have validated the suitability of this technique and have demonstrated significant effects of barbiturates, ethanol, and "stress" on benzodiazepine receptors in vivo.