Differential Effects of Antidepressants in Adult and Developing Animals

描述（由申请方提供）：尽管有大量关于抗抑郁药在成年动物中的分子、神经化学和行为效应的数据，但关于抗抑郁药在幼年动物中的效应知之甚少。我们知识上的这一差距特别令人关切。不仅有研究表明，抑郁的青少年对抗抑郁药的反应与成年人不同，青少年对三环类抗抑郁药的反应特别差或缺乏抗抑郁药，而且抗抑郁药可能会引起行为后遗症（例如，自杀倾向）在青少年中更为突出。基于这些观察，我们建议比较和对比抗抑郁药在幼年和成年动物的药理作用。我们以前已经表明，在成年动物中发现的一些抗抑郁药的适应性反应不会发生在幼年/青春期动物中。相比之下，我们的初步数据表明，减少不动的强迫游泳测试，行为测试反应，用于预测抗抑郁药的临床效果，发生在青少年动物与地昔帕明，三环类抗抑郁药治疗，尽管临床观察，三环类药物不工作，以及在青少年抑郁症的治疗。我们建议比较和对比青少年和成人适应性神经内分泌和行为反应两类抗抑郁药，三环类药物和选择性5-羟色胺再摄取抑制剂。相关性：抑郁症是全球疾病负担的重要组成部分。拟议研究的结果将提供关于抗抑郁药与行为和脑化学变化相关的作用机制的新的重要信息，有助于解释临床发现，并有助于推动未来成人和青少年抑郁症的基础和临床研究。

DESCRIPTION (provided by applicant): Although there is a wealth of data on the molecular, neurochemical and behavioral effects of antidepressants in adult animals, very little is known about the effects of antidepressants in juvenile animals. This gap in our knowledge is of particular concern. Not only have studies shown that depressed adolescents do not respond to antidepressants in the same fashion as do adults, with youngsters showing a particularly poor or lack of antidepressant response to tricyclic antidepressants, but antidepressants might induce behavioral sequelae (e.g., suicidality) that are more prominent in youngsters. Based upon these observations, we propose to compare and contrast the pharmacologic effects of antidepressants in juvenile and adult animals. We previously have shown that some of the adaptive responses to antidepressants that are found in adult animals do not occur in juvenile/adolescent animals. In contrast, our preliminary data suggest that reduced immobility in the forced swim test, a behavioral test response used to predict the clinical effects of antidepressants, occurs in adolescent animals treated with desipramine, a tricyclic antidepressant, despite the clinical observations that tricyclics do not work well in youngsters for treatment of depression. We propose to compare and contrast juvenile and adult adaptive neuroendocrine and behavioral responses to two classes of antidepressants, tricyclics and selective serotonin re-uptake inhibitors. Relevance: Depression contributes markedly to the burden of disease world-wide. The results of the proposed studies will provide new and important information on the mechanisms of action of antidepressants in relation to changes in behavior and brain chemistry, assist in the interpretation of clinical findings, as well as help to drive future basic and clinical research in depression in both adults and adolescents.