Differential Effects of Antidepressants in Adult and Developing Animals

抗抑郁药对成年动物和发育中动物的不同作用

• 批准号: 7135486
• 负责人: Robert Nelson Pechnick
• 金额: $ 17.89万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7135486
• 关键词: adrenocorticotropic hormone; age difference; amitriptyline; antidepressants; behavior test; corticosterone; corticotropin releasing factor; desipramine; functional ability; gene expression; hypothalamic pituitary adrenal axis; juvenile animal; laboratory rat; mature animal; neuroendocrine system; paroxetine; pharmacokinetics; psychopharmacology; sertraline

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.

描述（由申请人提供）：尽管有大量关于抗抑郁药对成年动物的分子、神经化学和行为影响的数据，但关于抗抑郁药对幼年动物的影响却知之甚少。我们的知识差距尤其值得关注。研究不仅表明，抑郁症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抗抑郁反应特别差或缺乏，而且抗抑郁药可能会引起行为后遗症（例如自杀），这种后遗症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中的药理作用。我们之前已经证明，成年动物对抗抑郁药的一些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，在用三环类抗抑郁药地昔帕明治疗的青少年动物中，强迫游泳测试（一种用于预测抗抑郁药临床效果的行为测试反应）中的不动性降低，尽管临床观察表明三环类药物在治疗青少年抑郁症方面效果不佳。我们建议比较和对比青少年和成人对两类抗抑郁药、三环类药物和选择性血清素再摄取抑制剂的适应性神经内分泌和行为反应。相关性：抑郁症显着加重了全世界的疾病负担。拟议研究的结果将提供有关抗抑郁药与行为和大脑化学变化相关的作用机制的新的重要信息，有助于解释临床结果，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。