REM SLEEP DEPRIVATION AND DEPRESSION

这项拟议研究的长期目标是寻找大脑 调节人类疾病发生和改善的过程 内源性抑郁(ED)。在以前的工作中，我们发现有几个 给新生大鼠服用抗抑郁药物后，产生了 模拟行为和快速眼动睡眠特征的成年大鼠的“抑郁” 人类勃起功能障碍，并通过传统的抗抑郁药物治疗得到改善。 这项拟议的研究将检验有关人类大脑媒介的假设。 ED及其在该动物模型中的改进。人与动物 研究结果表明，改变的5-羟色胺(5-羟色胺)神经传递或 REM睡眠改变可能是ED及其改善的脑介质。这个 关于抑郁症5-羟色胺介体的拟议动物研究将检验假说 这种ED是通过(A)脑内5-羟色胺单位放电频率降低而起作用的。 中缝背核(DRN)；或(B)随机的而不是有序的5HT单位 DRN的放电频率；或5HT1和/或5HT2受体上调 DRN和大脑皮层。关于快速眼动睡眠调节剂的拟议动物工作 抑郁症将检验ED是由神经元介导的假设 ED患者快速眼动睡眠增加的底物，即增加的放电率 巨细胞被盖区的胆碱感受性单位。我们会 确定是否这些假想的介体中的任何一个导致了大鼠 抑郁通过以下几个方面表现出来：(1)中介会表现出共同的效应 几种不同的抗抑郁药物用于新生儿生产 ED；(2)脑内致病介质的个体差异 与大鼠抑郁的个体差异相关；(3) 抗抑郁药物治疗将逆转发现的异常 发病的中介物。我们假设改善的调停者 是抑郁症的DRN或FTG的相反(相反)介体。动物 改善ED的研究将涉及丙咪嗪对动物的影响 抑郁症。我们将确定是否改善两者之间的关系。和 在动物的REM睡眠变量之间的关系是相同的 以前在人类中发现的改善和快速眼动睡眠变量。如果是的话， 这将是大脑调节动物进步的证据 在人类身上进行操作。这项拟议的工作可能会阐明大脑的基础 人类勃起功能障碍的发病机制及其改善 预防和成功治疗。

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.