MONOAMINE INTERACTIONS AND ANTIDEPRESSANT DRUGS

单胺相互作用和抗抑郁药物

• 批准号: 6556826
• 负责人: Michelle E Page
• 金额: $ 7.5万
• 依托单位: MCP HAHNEMANN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-05 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6556826
• 关键词: amines; antidepressants; behavior test; behavioral /social science research tag; drug administration rate /duration; drug interactions; frontal lobe /cortex; hippocampus; laboratory rat; microdialysis; norepinephrine; psychopharmacology; serotonin; serotonin inhibitor; stressor

DESCRIPTION (adapted from applicant's abstract): Much evidence exists to support the interrelationship between dysfunction of the monoamine neurotransmitter systems, stress and the onset of depressive illness. For years research suggested disruption of the noradrenergic response to stress as the predisposing factor in depression. This was based on animal studies describing depletion of norepinephrine (NE) in response to severe stressors coupled with clinical evidence that many compounds which increased NE were effective in reducing the symptoms associated with this disorder. Due in part to the many adverse side effects associated with tricyclic antidepressants, newer more selective compounds were developed and the success of the serotonin (5-HT) selective reuptake inhibitors (SSRIs) as antidepressants shifted the focus of the field to re-examine the role of serotonin in depression. This is the most widely prescribed class of antidepressants today. However, there is a paucity in the knowledge of how all antidepressants exert therapeutic action. A continued effort to understand the mechanism of action of antidepressants is now focused on the interrelationship of NE and 5-HT. The proposed research program will attempt to provide evidence for important interactions between these two neurotransmitter systems that may help to explain the ability of diverse pharmacological agents to exert similar clinical benefits. Specifically, studies will examine the hypothesis that even though selective neuronal transporter inhibitors may act specifically when administered acutely, they will have indirect actions on other systems following chronic administration. This ability to alter multiple monoamine systems after chronic drug administration may account for the delay in therapeutic effects. Additionally, a nonselective reuptake inhibitor, venlafaxine, will be compared with the NE-selective inhibitor reboxetine and the 5-HT selective reuptake inhibitor fluoxetine to determine whether there is a basis for nonselective monoamine reuptake inhibition to confer greater therapeutic benefits. In addition, experiments will be performed to examine the hypothesis that both 5-HT and NE systems mediate behavioral responses to swim stressor. Furthermore, the impact of chronic antidepressant treatment on the behavioral responses and neurochemical effects associated with the swim stressor will be explored. The results of the proposed studies will provide insight into neuronal adaptations of two monoamine neurotransmitter systems that have been implicated in depression and be useful in the development of therapeutic agents for the treatment of depression.

描述（根据申请人的摘要改编）：有很多证据存在于 支持单胺功能障碍之间的相互关系 神经递质系统，压力和抑郁症的发作。多年 研究表明，去甲肾上腺素对压力的反应破坏了 抑郁症中的易感性因素。这是基于描述的动物研究 响应严重的应激源与重度的耗尽 临床证据表明，许多NE的化合物有效 减少与这种疾病相关的症状。部分原因是 与三环抗抑郁药相关的不良副作用，更新 开发了选择性化合物，5-羟色胺（5-HT）的成功 选择性再摄取抑制剂（SSRIS）随着抗抑郁药的重点移动 重新检查5-羟色胺在抑郁症中的作用的领域。这是最大的 如今，广泛规定的抗抑郁药类别。但是，很少 了解所有抗抑郁药如何发挥治疗作用。一个 继续努力了解抗抑郁药的作用机理是 现在专注于NE和5-HT的相互关系。拟议的研究 计划将尝试提供证据证明 这两个神经递质系统可能有助于解释 不同的药理学剂具有类似的临床益处。 具体而言，研究将研究以下假设 神经元转运蛋白抑制剂急性施用时可能会特别起作用， 他们将在慢性之后对其他系统采取间接操作 行政。这种能够改变慢性后多种单胺系统的能力 药物管理可以解释治疗作用的延迟。 此外，将比较一种非选择性的再摄取抑制剂Venlafaxine 与NE选择性抑制剂重羧酸氨酸和5-HT选择性再摄取 抑制剂氟西汀确定是否存在非选择性的基础 单胺再摄取抑制以赋予更大的治疗益处。在 此外，还将进行实验以检查两个假设 5-HT和NE系统介导对游泳应力源的行为反应。此外， 慢性抗抑郁治疗对行为反应的影响 将探索与游泳应力相关的神经化学作用。这 拟议研究的结果将提供对神经元适应的见解 与已涉及的两个单胺神经递质系统 抑郁症，可用于开发治疗剂 抑郁症的治疗。

项目成果

Simultaneous analyses of the neurochemical and behavioral effects of the norepinephrine reuptake inhibitor reboxetine in a rat model of antidepressant action.

同时分析去甲肾上腺素再摄取抑制剂瑞波西汀在抗抑郁作用大鼠模型中的神经化学和行为影响。

• DOI: 10.1007/s00213-002-1269-x
• 发表时间: 2003
• 期刊: Psychopharmacology.
• 作者: Page,MichelleE;Brown,Kevin;Lucki,Irwin
• 通讯作者: Lucki,Irwin

Effects of acute and chronic reboxetine treatment on stress-induced monoamine efflux in the rat frontal cortex.

急性和慢性瑞波西汀治疗对应激诱导的大鼠额叶皮层单胺流出的影响。

• DOI: 10.1016/s0893-133x(02)00301-9
• 发表时间: 2002
• 期刊: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
• 作者: Page,MichelleE;Lucki,Irwin
• 通讯作者: Lucki,Irwin