REM SLEEP DEPRIVATION AND DEPRESSION

快速眼动睡眠剥夺和抑郁

• 批准号: 3379434
• 负责人: GERALD W VOGEL
• 金额: $ 19.35万
• 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 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3379434
• 关键词: albino rat; antidepressants; behavior disorders; beta adrenergic receptor; disease /disorder model; dorsal raphe nucleus; drug administration rate /duration; electrophysiology; imipramine; infant animal; locus coeruleus; mature animal; psychopharmacology; receptor binding; receptor sensitivity; serotonin receptor; sleep deprivation

Our prior work supportedthe validity of a new animal model of endogenous depression. Rats treatedneonatally with cloimipramine (CLI) developed a delayed adult "depression" with behavioral abnormalities, REM sleep abnormalities, and treatment responses similar to those of endogenous depression. Recent work indicates that other antidepressant drugs, administered neonatally to rats, also produce adult depressive behaviors. The goal of the proposed work is to shed light on brain processes involved in the cause and improvement of the animal "depression". The first is that administered to neonatal rats, antidepressant drugs result in a long term down-regulation of amine receptors (5HT2 and beta adrenergic) and/or diminution of aminergic nerve impulses in noradrenergic (NA) neurons of the locus coeruleus and serotonergic (5HT) neurons of the dorsal raphe nucleus. The animals are then deprived of behavioral stimulation provided by monoamines and become depressed. Our specific aims are to test this hypothesis by determining whether several antidepressant drugs, administered to neonatal rats have a common lowering effect on the above amine receptors in neonates or in adult "depressed" rats and also decrease aminergic nerve impulses in the adult. Such a common effect of different causes of depression would be a likely pathway that mediates the depression. The second hypothesis about pathogenesis is that the antidepressant drugs cause the later depression by neonatal REM sleep deprivation (RSD) without a REM rebound. All antidepressant drugs whose neonatal administration causes later depressive behaviors produce neonatal RSD without immediate REM rebound. Our specific aim is to thest theis hypothesis by detgermining whether (1) normalizing REM sleep levels in CLI treated neonatal rats will prevent the later depresnormalizing REM sleep levels in CLI treated neonatal rats will prevent the later depression; and (2) inducing a neonatal REM rebound immediately after CLI will prevent the later depression. As mentioned, another long term goal of the work is to investigate brain processes that mediate the improvement of the depression. Our specific aim is to test the hypothesis that in adult "depressed" rats several efficacious antidepressant treatments have a common effect on amine receptors or aminergic neuronal impulses. Again, such a common effect of different treatmentswould bea likely mediatorof improvement.A positive finding in the proposed work would producea powerful tool for future research and may shedlight on the causes and treatment of endogenous depression.

我们先前的工作支持了内源性新动物模型的有效性 沮丧。用氯氨基胺（CLI）治疗的大鼠开发了 延迟成人“抑郁”，行为异常，雷姆睡眠 异常和类似于内源性的治疗反应 沮丧。最近的工作表明其他抗抑郁药， 向大鼠新生儿施用，还会产生成人抑郁行为。 拟议工作的目的是阐明大脑过程 参与动物“抑郁”的原因和改善。这 首先是对新生大鼠的施用，抗抑郁药结果 长期下调胺受体（5HT2和β 肾上腺素能）和/或氨基神经冲动的减少 基因座核和5-羟色胺能（5HT）的甲肾上腺素能神经元（Na）神经元 背raphe核的神经元。然后将动物剥夺 单胺提供的行为刺激并变得沮丧。我们的 具体目的是通过确定是否有几个 给新生大鼠施用的抗抑郁药有一个常见的 降低对新生儿或成年胺受体的影响 “抑郁”大鼠，也减少成人的氨基神经冲动。 抑郁症原因的这种常见影响可能是 介导抑郁症的途径。第二个关于 发病机理是抗抑郁药导致后期抑郁症 通过新生儿REM睡眠剥夺（RSD），没有REM反弹。全部 抗抑郁药，其新生儿给药稍后引起 抑郁行为会产生新生儿RSD，而无需立即反弹。 我们的具体目的是通过替代（1）来替代theis假设。 在经过CLI治疗的新生大鼠中标准化REM睡眠水平将阻止 CLI治疗的新生儿大鼠中后来的重新归置REM睡眠水平 将防止后来的抑郁症； （2）诱导新生儿REM 在CLI之后立即反弹将防止后来的抑郁症。作为 提到，这项工作的另一个长期目标是调查大脑 介导抑郁症改善的过程。我们的具体 目的是检验以下假设：成年人“抑郁”大鼠几个 有效的抗抑郁药对胺有共同的影响 受体或氨基神经元脉冲。再次，如此常见的效果 不同的治疗可能会改善介体。 在拟议的工作中寻找将为未来生成强大的工具 研究和可能会出现内源性的原因和治疗 沮丧。