REM SLEEP DEPRIVATION AND DEPRESSION

快速眼动睡眠剥夺和抑郁

• 批准号: 2415893
• 负责人: GERALD W VOGEL
• 金额: $ 23.99万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2415893
• 关键词: REM sleep; antidepressants; arousal; biological models; brain electrical activity; clinical depression; dorsal raphe nucleus; electroencephalography; imipramine; laboratory rat; mature animal; newborn animals; open field behavior; phenelzine; polygraphy; receptor binding; receptor sensitivity; reticular formation; self stimulation; serotonin; serotonin receptor; sex behavior; sleep; sleep deprivation; wakefulness

The broad long term objectives of the proposed research are to find brain processes that mediate the pathogenesis and the improvement of human endogenous depression (ED). In previous work we found that several antidepressant drugs, administered to neonatal rats, produced a "depression" in adult rats that modelled behavioral and REM sleep features of human ED and that improved with conventional antidepressant treatments. The proposed research will test hypotheses about brain mediators of human ED and its improvement in this animal model of ED. Human and animal findings suggest that altered serotonergic (5HT) neurotransmission or altered REM sleep may be brain mediators of ED and its improvement. The proposed animal work on 5HT mediators of depression will test hypotheses that ED is mediated by (a) decreased firing rates of 5HT units in the dorsal raphe nucleus (DRN); or (b) random rather than ordered 5HT unit firing rate in the DRN; or upregulation of 5HT1 and/or 5HT2 receptors in the DRN and cortex. The proposed animal work on REM sleep mediators of depression will test the hypothesis that ED is mediated by a neuronal substrate of increased REM sleep found in ED, viz increased firing rate of cholinoceptic units in the gigantocellular tegmental field (FTG). We will determine whether any of these hypothesized mediators cause the rat depression by the following: (1) mediators will show a common effect of several different antidepressant drugs administered to neonates to produce ED; (2) individual differences in brain mediators of pathogenesis will correlate with individual differences in rat depression; (3) antidepressant drug treatments will reverse abnormalities found in mediators of pathogenesis. We hypothesize that mediators of improvement are reversals (opposites) of DRN or FTG mediators of depression. Animal studies of improvement of ED will involve effects of imipramine on animal depression. We will determine whether relation between improvement. and REM sleep variables in animals is the same as the relation between improvement and REM sleep variables previously found in humans. If so, this will be evidence that brain mediators of improvement in animals operate in humans. The proposed work may illuminate brain substrates of pathogenesis and improvement of human ED and thereby contribute to its prevention and successful treatment.

拟议研究的广泛长期目标是找到大脑 介导人的发病机理和改善的过程 内源性抑郁症（ED）。 在以前的工作中，我们发现有几个 给新生大鼠施用的抗抑郁药产生了A 成年大鼠的“抑郁”，以行为和REM睡眠特征进行建模 人类ED和传统抗抑郁药的改善。 拟议的研究将检验有关人类脑介导者的假设 ED及其在这种ED动物模型中的改善。 人类和动物 调查结果表明，更改血清素能（5HT）神经传递或 REM睡眠改变可能是ED的脑介质及其改善。 这 拟议的动物工作在5HT抑郁症的介体上将检验假设 该ED是由（a）降低的5HT单位的点火率介导的 背raphe核（DRN）;或（b）随机而不是有序的5HT单位 DRN的发射率；或在5HT1和/或5HT2受体中上调 DRN和皮层。 拟议的动物在REM睡眠介体中的作品 抑郁将检验以下假设，即ED是由神经元介导的 ED中发现的REM睡眠增加的底物，即发射率提高 Gigantocellular换段磁场（FTG）中的胆碱感应单元。 我们将 确定这些假设的介体是否引起大鼠 抑郁以下以下内容：（1）调解员将显示出的共同作用 给新生儿施用的几种不同的抗抑郁药产生 ed; （2）发病机理脑介导者的个体差异将 与大鼠抑郁症的个体差异相关； （3） 抗抑郁药治疗将逆转异常 发病机理的介体。我们假设改进的调解人 是DRN或FTG抑郁介质的逆转（对立）。 动物 ED改善的研究将涉及丙咪嗪对动物的影响 沮丧。 我们将确定改进之间的关系。和 动物的REM睡眠变量与 先前在人类中发现的改善和REM睡眠变量。 如果是这样， 这将证明动物改善的脑介质 在人类中运作。 拟议的工作可能会照亮 人ED的发病机理和改善，从而有助于其 预防和成功治疗。