PLATELET ADRENORECEPTOR DESENSITIZATION IN DEPRESSION

抗抑郁药作用机制的研究进展 化合物表明，长时间的药物治疗会导致 脑α2的脱敏(即反应性降低) 肾上腺素受体。在一定程度上，基于这一发现，“监管失调” 抑郁症的病因学理论最近被提出。 前进(1)。这一理论在一定程度上表明，一个特征 抑郁疾病的易感性可能是由于 反馈抑制型α2肾上腺素能受体的调节 大脑。抑郁症患者α2肾上腺素能受体的评估 因此，患者可能会提供抑郁症的遗传标记。 生病了。我的提案将评估Alpha2肾上腺素受体是否 很容易在血小板上表现出特征，可能为 开发出这样一种标记。在一项对20名抑郁症患者的研究中 和20个对照，我希望提供初步证据 血小板α2肾上腺素受体的测定作为有用的标志物 用于诊断、治疗和/或预防复发 为抑郁症患者准备的。我的方法将与前面的方法不同 报告了关于两者之间的联系的模棱两可的发现的研究 血小板肾上腺素受体与抑郁症的临床指标(18)。 早期的研究报告只有一次静态测量 肾上腺素受体状态。相反，我建议研究这一动态 激动剂诱导的肾上腺素能受体脱敏过程。我的 研究将使用~3H-对氨基可乐定来比较 血小板肾上腺素能受体最大脱敏程度 患者和对照组之间的悬浮期。我们将尝试 确定(A)是否改变了血小板的脱敏作用 未经治疗的患者与未经治疗的对照组的比较，(B) 治疗后脱敏反应是否发生变化 地塞帕明，以及(C)在字母2中是否有差异 应答者和非应答者之间的肾上腺素受体脱敏 DMI治疗的应答者。

Research concerning the mode of action of antidepressant compounds has indicated that prolonged drug treatment leads to desensitization (i.e. decreased responsiveness) of brain alpha2 adrenoceptors. Based partly on this finding, a "dysregulation" theory for the etiology of depressive illness was recently put forward (1). That theory suggests, in part, that a trait vulnerability for depressive illness could be due to a faulty regulation of feedback-inhibitory alpha2 adrenoceptors in the brain. An assessment of alpha2 adrenoceptors from depressed patients may therefore provide a genetic marker for depressive illness. My proposal will assess whether alpha2 adrenoceptors as readily characterized on platelets, might offer the substrate for developing such a marker. In a study with 20 depressed patients and 20 controls, I hop to provide preliminary evidence for measurement of platelet alpha2 adrenoceptors as a useful marker for either the diagnosis, treatment and/or prevention of relapse for depressed patients. My approach will be unique from earlier studies which have reported equivocal findings on a link between platelet adrenoceptors and clinical indices of depression (18). Earlier studies reported only single time "static" measurements of adrenoceptor status. Instead, I propose to study the dynamic process of agonist-induced adrenoceptor desensitization. My studies will use 3H-para-aminoclonidine to compare the rate and maximal degree of adrenoceptor desensitization in platelet suspensions between patients and controls. It will be attempted to ascertain (A) whether desensitization is altered in platelets from untreated patients compared to untreated controls, (B) whether desensitization changes following treatment with desipramine, and (C) whether there are differences in alpha2 adrenoceptor desensitization between responders and non- responders to treatment with DMI.