ONTOGENY OF DEPRESSIVE SUBSTRATES

抑郁基质的个体发育

• 批准号: 6185845
• 负责人: GERALD W VOGEL
• 金额: $ 16.18万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6185845
• 关键词: REM sleep; age difference; aggression; aging; behavior test; clomipramine; developmental psychology; imipramine; laboratory rat; major depression; newborn animals; pathologic process; polysomnography; sex behavior; sleep deprivation

DESCRIPTION (Adapted from applicant's abstract): The long-term goal of the proposed work is to determine brain processes involved in the pathogenesis of endogenous depression (ED). In past work investigator found that if neonatal rats were treated with clomipramine (CLI) and other antidepressant drugs they developed signs of depression when they became adults. The investigator's current work concerns the brain substrates of the adult rat depression. The work proposed in this application concerns the processes between neonatal CLI administration and the adult depression. The investigator's question is: what neonatal effect of CLI leads to the adult depression? Evidence suggests that neonatal RSD by CLI (and other antidepressant drugs) produces the adult depression. The investigator has recently developed the first successful technique to produce long-term, instrumental REM sleep deprivation (IRSD). Using this technique, his main aim is to test the hypothesis that in rats neonatal RSD causes adult depression (RSD hypothesis). An unambiguous test of the RSD hypothesis requires that IRSD be administered to neonatal rats over the precise age period (critical period) of depressogenic CLI administration to other rats. The precise critical age period of CLI administration has not been determined. Thus, preliminary to the IRSD study, the investigator's first aim is to determine the precise critical neonatal age period of depressive CLI administration. Also an unambiguous test of the RSD hypothesis requires that IRSD achieve the same RSD as neonatal CLI. The level of RSD by CLI has not been precisely determined. Thus, preliminary to the IRSD study, the investigator's second aim is to determine the precise level of daily RSD produced by neonatal CLI during the prior established precise critical period of CLI administration. Using these 2 results, he will administer IRSD to test the RSD hypothesis. Several adult behavior and RS measures related to depression will be the outcome measures. Although it is known from brief (1-3 hour) samples that RS time decreases in the first postnatal month, very little is known about the ontogeny of other RS variables and the interrelationships of their developmental changes. The investigator has recently developed the first successful technique for continuous (24 hour/ day), long-term (weeks) polysomnographic (PSG) recording of sleep/wake states in neonatal rats. With this technique the investigator's preliminary evidence suggests that 7 different RS variables follow parallel developmental courses over postnatal weeks 2-4. Confirmation of this preliminary finding can: a) yield the first systematic data on the ontogeny of several different RS parameters; b) identify the RS markers of the critical period of depressive CLI administration; c) suggest by these RS markers and their known neurophysiology and neurochemistry testable hypotheses about the underlying processes involved in the ontogeny of depressive disposition. The significance of the proposed work is that it may shed light on early developmental processes that contribute to later depression and depressive temperament. In doing so, the proposed work may help in the search for early prevention of ED, and in more precisely targeted treatments of ED.

描述（根据申请人的摘要改编）： 建议的工作是确定发病机理涉及的大脑过程 内源性抑郁症（ED）。 在过去的工作中，调查员发现 新生大鼠用氯米帕明（CLI）和其他抗抑郁药处理 他们成年后，他们会出现抑郁症的迹象。 这 研究者目前的工作涉及成年老鼠的大脑底物 沮丧。 本应用程序中提出的工作涉及过程 在新生儿CLI给药和成人抑郁症之间。 这 研究者的问题是：CLI的新生儿影响导致成人 沮丧？ 有证据表明CLI的新生儿RSD（以及其他 抗抑郁药）产生成人抑郁症。 调查员有 最近开发了第一种成功的技术来生产长期， 工具性REM睡眠剥夺（IRSD）。 使用这种技术，他的主要 目的是检验以下假设：新生儿RSD导致成人 抑郁（RSD假设）。 RSD假设的明确检验 要求在确切年龄范围内将IRSD施用到新生大鼠 对其他大鼠的降压CLI给药期（关键时期）。 CLI给药的确切关键年龄段尚未 决定。 因此，对IRSD研究的初步研究是研究者的第一个 目的是确定抑郁症的精确关键新生儿年龄 CLI给药。 还需要对RSD假设进行明确的测试 IRSD达到与新生儿CLI相同的RSD。 CLI的RSD水平 不能精确确定。 因此，对IRSD研究的初步 研究者的第二个目的是确定每日RSD的精确水平 由新生儿CLI在先前确定的精确临界时产生 CLI给药期。 使用这两个结果，他将管理 IRSD检验RSD假设。 几种成人行为和RS措施 与抑郁有关的结果将是结果措施。 虽然已知 从短暂的（1-3小时）样品中，RS时间在产后第一次减少 一个月，关于其他RS变量的个体发育范围很少 其发展变化的相互关系。 调查员有 最近开发了第一种连续的成功技术（24小时/ 一天），长期（周）多个学位学（PSG）睡眠/唤醒记录 新生大鼠的状态。 使用此技术，研究者的初步 有证据表明7种不同的RS变量并行遵循 出生后第2-4周的发展课程。 确认这一点 初步发现可以：a）产生有关个体发育的第一个系统数据 几个不同的RS参数； b）确定RS标记 抑郁CLI给药的关键时期； c）这些RS建议 标记及其已知的神经生理学和可检验的神经化学 关于与个体发育的基础过程的假设 抑郁的处置。 拟议工作的重要性是 可能会阐明有助于以后的早期发展过程 抑郁和抑郁气质。 这样，拟议的工作可能 帮助寻找早期预防ED，更准确地说 ED的目标治疗。