RECEPTORS IN THE CENTRAL NERVOUS SYSTEM--BIOCHEMISTRY TO BEHAVIOR

苯二氮卓类药物与特定神经细胞膜的相互作用 受体启动一系列神经元事件，导致 增强GABA介导的氯离子通透性。这个 后者的主要药理作用在行为上的结果 苯二氮类药物，即其抗焦虑、抗惊厥、催眠 和肌肉松弛作用。除了苯二氮类药物外，还有一种 小镇静剂类镇静催眠药的种类 (例如巴比妥酸盐)似乎与一个或多个 苯二氮卓类/GABA受体复合体的成分，以及 因此，后者已被提议作为未成年人的共同场所 镇静剂的作用。苯二氮卓/γ-氨基丁酸的几个方面 受体复合体目前正在研究中。最近的工作有 使用体外系统测量GABA受体- 大鼠脑亚细胞制剂中效应器的偶联 突触神经元)。这项技术极大地促进了研究 GABA受体偶联氯离子的调节作用 频道。利用这种方法，我们研究了相互作用。 乙醇与GABA受体复合体的研究发现 乙醇、相关短链醇和几种麻醉剂 药物能够刺激这种受体，并且在 与药理相关的浓度。在相关研究中，我们 已鉴定出一种新的咪唑苯并二氮类药物Ro15-4513，它 阻断乙醇对GABA受体的体外作用 介导的~(36)C-摄取以及许多行为效应 乙醇。长期给予大鼠酒精可导致大鼠 大鼠脑内GABA受体介导的~(36)Cl摄取减少 突触神经体，这种效应是可逆的，因为它不是 观察酒精戒断综合征后的情况。在其他研究中 我们已经检查了放射性标记的苯二氮卓类药物的用途。 测定苯二氮类药物的受体拮抗剂Ro15-1788 活体内的受体。我们的结果验证了该方法的适用性。 这项技术和已经证明了显著的效果 巴比妥酸盐，自然产生的类固醇激素，乙醇和 体内苯二氮卓类受体的“应激”。

Benzodiazepines interact with a specific neuronal membrane receptor to initiate 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 studies. Recent work has employed 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 the regulation of the GABA receptor-coupled chloride ion channel. Using this method, we have studied the interaction of ethanol with the GABA receptor complex and have found that ethanol, related short-chain alcohols and several anesthetic agents are capable of stimulating this receptor and at pharmacologically-relevant concentrations. In related studies we have identified a novel imidazobenzodiazepine, Ro15-4513, which blocks both the in vitro effects of ethanol on GABA receptor- mediated 36C1- uptake as well as many of the behavioral effects of ethanol. Chronic administration of ethanol to rats results in a decrease in GABA receptor-mediated 36Cl-uptake in synaptoneurosomes, an effect that is reversible since it is not observed after the ethanol withdrawal syndrome. 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, naturally-occurring steroid hormones, ethanol and "stress" on benzodiazepine receptors in vivo.