ADRENERGIC NERVE FUNCTION AFTER PSYCHOTROPIC DRUGS

服用精神药物后的肾上腺素能神经功能

• 批准号: 3375823
• 负责人: CHARLES B SMITH
• 金额: $ 6.03万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-09-15 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3375823
• 关键词: 3 methoxy 4 hydroxyphenylethyleneglycol; antidepressants; brain; brain electronic stimulator; catecholamines; cell membrane; clinical anxiety; clonidine; disease /disorder classification; high performance liquid chromatography; human subject; human therapy evaluation; longitudinal animal study; longitudinal human study; mental disorder chemotherapy; neurochemistry; neurotransmitter metabolism; norepinephrine; platelets; prazosin; psychobiology; psychopharmacology; psychotropic drugs; yohimbine

Presynaptic receptors are important in the regulation of transmitter release from various neurons. The project is based upon the following hypotheses: 1) presynaptic alpha2 adrenergic receptors in the central nervous system are important sites for the pharmacological actions of psychotropic drugs, especially those agents which are used to treat endogenous depression and panic-anxiety disorder; 2) depressive disorders and anxiety disorders might be related to abnormal presynaptic alpha2 adrenergic receptor function; 3) the status of these receptors might be reflected by alpha2 adrenergic receptors on blood platelet membranes as well as by responses to physiological and pharmacological challenges. Functional changes in presynaptic alpha2 adrenergic receptors will be determined in 1) superfused, electrically stimulated rat brain slices and 2) isolated rat left atrial strips. The release of neurotransmitter during electrical stimulation of neurons in these preparations will be determined by mesuring a) the release of 3H-norepinephrine after preincubating the tissues with 3H-norepinephrine, b) the efflux of endogenous norepinephrine by a combination of high pressure liquid chromatography and electrochemical detection, c) changes in the responses of the isolated atrial muscle preparation, and d) the release of dopamine beta-hydroxylase. Simultaneously with the functional studies the specific binding of 3H-clonidine, 3H-yohimbine, 3H-prazosin and 3H-dihydroalprenolol to neuronal membranes isolated from various areas of the rat brain and to neuronal and non-neuronal membranes isolated from heart and vascular smooth muscle will be measured. Studies to determine functional changes in post-synaptic alpha2 adrenergic receptors will be carried out with isolated strips of rat tail artery. Changes in the number and/or affinity of alpha2 adrenergic receptors on human blood platelet membranes will be determined in depressed patients and patients with anxiety disorders before, during and after treatment, as well as in normal subjects and in patients with other psychiatric and non-psychiatric diagnoses. The specific binding of various agonist and antagonist ligands for the alpha2 receptor on platelet membranes will be measured to assess alpha2 adrenergic receptor function. In addition, changes in various cardiovascular parameters and in plasma catecholamine levels will be determined in these patients after physiological (assuming an erect position from a supine position) and pharmacological (intravenous yohimbine infusions) challenges.

突触前受体在调节中很重要 从各种神经元释放。 该项目基于以下 假设：1）中央突触前α2肾上腺素能受体 神经系统是针对药理学作用的重要部位 精神药物，尤其是那些用于治疗的药物 内源性抑郁和恐慌症； 2）抑郁症 和焦虑症可能与异常突触前α2有关 肾上腺素能受体功能； 3）这些受体的状态可能是 由血小板膜上的α2肾上腺素能受体反射为 以及对生理和药理挑战的反应。 突触前α2肾上腺素能受体的功能变化将是 在1）超级掺杂的，电刺激的大鼠脑切片和 2）孤立的大鼠左心脏条。 神经递质在 将确定这些制剂中神经元的电刺激 通过汇总a）预孵育后，释放3H-脱甲肾上腺素 具有3H-脱甲肾上腺素的组织，b）内源性去甲肾上腺素的排出 通过高压液相色谱和电化学的组合 检测，c）孤立心房肌肉的反应变化 制备和d）多巴胺β-羟化酶的释放。 同时与功能研究的特定结合 3H-克罗尼定，3H-Yohimbine，3h- prazosin和3h-二氢丙二醇 从大鼠大脑的各个区域分离出来的神经元膜， 神经元和非神经元膜从心脏和血管平滑 将测量肌肉。 确定功能变化的研究 突触后α2肾上腺素能受体将与孤立的 大鼠尾动脉的条。 alpha2的数量和/或亲和力的变化 将确定人血小板膜上的肾上腺素能受体 在抑郁症患者和患有焦虑症的患者之前，之前 治疗后以及正常受试者和患者 其他精神病和非精神诊断。 特定的结合 血小板上α2受体的各种激动剂和拮抗剂配体 将测量膜以评估α2肾上腺素能受体功能。 此外，各种心血管参数的变化和等离子体的变化 在这些患者之后，将确定儿茶酚胺水平 生理学（假设从仰卧位置竖立）和 药理（静脉注射Yohimbine输注）挑战。