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）：尽管有大量有关抗抑郁药在成年动物中的分子，神经化学和行为影响的数据，但对抗抑郁药在少年动物中的影响知之甚少。我们所知的差距特别关注。不仅研究表明，抑郁症的青少年与成年人没有对抗抑郁药的反应，年轻人表现出对三环类抗抑郁药特别较差或缺乏抗抑郁药反应，但抗抑郁药可能会诱导行为后遗症（例如，自杀性）在年轻人中更为突出。基于这些观察结果，我们建议比较和对比少年和成年动物抗抑郁药的药理作用。我们以前已经表明，在成年动物中发现的一些自适应反应在少年/青少年动物中不会发生。相比之下，我们的初步数据表明，强制游泳测试中的固定性降低，这是一种行为测试反应，用于预测抗抑郁药的临床作用，发生在用苯甲胺治疗的青少年动物中，尽管苯甲胺是一种三环抗抑郁药，尽管临床观察结果在年轻人治疗抑郁症的临床观察结果中确实没有很好地作用。我们建议对两类抗抑郁药，三轮车和选择性5-羟色胺再摄取抑制剂进行比较和对比少年和成人自适应神经内分泌以及行为反应。相关性：抑郁症在全球范围内显着造成疾病负担。拟议研究的结果将提供有关抗抑郁药在行为和脑化学变化方面的作用机制的新的重要信息，有助于解释临床发现，并有助于推动成人和青少年抑郁症的未来基本和临床研究。