REGULATION OF HIPPOCAMPAL NEUROGENESIS BY ANTIDEPRESSANTS

抗抑郁药对海马神经发生的调节

基本信息

  • 批准号:
    7914988
  • 负责人:
  • 金额:
    $ 39.32万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-09-08 至 2010-08-31
  • 项目状态:
    已结题

项目摘要

This proposal examines how the regulation of adult neurogenesis produced by repeated antidepressant drug treatment in mice may contribute to behavioral recovery from stress and depression. Major depressive disorder results from convergent underlying genetic predispositons and exposure to environmental stress. Evidence for increases of neurogenesis in the adult dentate gyrus of the hippocampus are a model for changes in neuroplasticity that emerge with chronic treatment with antidepressant drugs and serve as a model for the production of therapeutic effects. Most studies have measured the effects of antidepressants using rodents under routine housing conditions and have ignored the critical role of genetics and stress in contributing to drug treatment effects. We have identified a mouse strain (MRL/MpJ) that shows larger increases in neurogenesis following chronic fluoxetine. Also, the addition of stress hormones augments the effects of fluoxetine on neurogenesis in a nonresponder mouse strain (C57BL/6). The central hypothesis of this grant proposal is that genetic predispositions and stress produce a critical role for revealing the effects of chronic antidepressant treatments on hippocampal neurogenesis. The use of flow cytometry as a technique to measure neurogenesis rapidly developed by this laboratory will enable completion of the large number of studies required for investigation of the pharmacology of neurogenesis. The primary goals of this proposal are: 1) demonstrate the critical role of exposure to corticosterone (CORT) in augmenting responses to chronic treatment with antidepressant drugs on neurogenesis and behavior in a responder and nonresponder mouse strain; 2) show whether environmental stress plays a similar role in causing antidepressant drugs to alter neurogenesis and behavior; and 3) determine whether hippocampal BDNF serves as a mechanism underlying
该提案探讨了成年神经发生的调节如何由 小鼠反复抗抑郁药物治疗可能有助于行为恢复 从压力和抑郁中解脱出来重度抑郁症是由于 潜在的遗传倾向和暴露于环境压力。证据 成年海马齿状回神经发生的增加是一个模型, 抗抑郁药物长期治疗后出现的神经可塑性变化 并作为产生治疗效果的模型。大多数研究 在常规饲养条件下, 忽视了遗传和压力在药物治疗中的关键作用 方面的影响.我们已经确定了一种小鼠品系(MRL/MpJ), 慢性氟西汀后的神经发生。另外,压力荷尔蒙的加入 增强氟西汀对无应答小鼠品系神经发生的作用 (C57BL/6)。这项拨款提案的核心假设是, 和应激对揭示慢性抗抑郁药的作用起关键作用 海马神经发生的治疗。使用流式细胞术作为一种技术, 这个实验室快速开发的神经发生测量将使完成 需要大量的研究来调查神经发生的药理学。 本提案的主要目标是:1)展示接触的关键作用 皮质酮(CORT)增强抗抑郁药长期治疗的反应 药物对应答和非应答小鼠品系的神经发生和行为的影响; 2) 显示环境压力是否在抗抑郁药物中起着类似的作用, 改变神经发生和行为; 3)确定海马BDNF是否 作为一种机制,

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Fluoxetine treatment induces dose dependent alterations in depression associated behavior and neural plasticity in female mice.
  • DOI:
    10.1016/j.neulet.2010.07.084
  • 发表时间:
    2010-10-22
  • 期刊:
  • 影响因子:
    2.5
  • 作者:
    Hodes GE;Hill-Smith TE;Lucki I
  • 通讯作者:
    Lucki I
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IRWIN LUCKI其他文献

IRWIN LUCKI的其他文献

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{{ truncateString('IRWIN LUCKI', 18)}}的其他基金

Kappa Receptor Antagonists as Rapid Acting Antidepressants
Kappa 受体拮抗剂作为速效抗抑郁药
  • 批准号:
    9030490
  • 财政年份:
    2016
  • 资助金额:
    $ 39.32万
  • 项目类别:
Kappa Receptor Antagonists as Rapid Acting Antidepressants
Kappa 受体拮抗剂作为速效抗抑郁药
  • 批准号:
    9753367
  • 财政年份:
    2016
  • 资助金额:
    $ 39.32万
  • 项目类别:
Buprenorphine for Depression and Anxiety
丁丙诺啡治疗抑郁和焦虑
  • 批准号:
    8451367
  • 财政年份:
    2012
  • 资助金额:
    $ 39.32万
  • 项目类别:
Buprenorphine for Depression and Anxiety
丁丙诺啡治疗抑郁和焦虑
  • 批准号:
    8627211
  • 财政年份:
    2012
  • 资助金额:
    $ 39.32万
  • 项目类别:
Buprenorphine for Depression and Anxiety
丁丙诺啡治疗抑郁和焦虑
  • 批准号:
    8710716
  • 财政年份:
    2012
  • 资助金额:
    $ 39.32万
  • 项目类别:
Buprenorphine for Depression and Anxiety
丁丙诺啡治疗抑郁和焦虑
  • 批准号:
    8239342
  • 财政年份:
    2012
  • 资助金额:
    $ 39.32万
  • 项目类别:
Regulation of Hippocampal Neurogenesis by Antidepressants
抗抑郁药对海马神经发生的调节
  • 批准号:
    8111695
  • 财政年份:
    2010
  • 资助金额:
    $ 39.32万
  • 项目类别:
Regulation of Hippocampal Neurogenesis by Antidepressants
抗抑郁药对海马神经发生的调节
  • 批准号:
    8471195
  • 财政年份:
    2010
  • 资助金额:
    $ 39.32万
  • 项目类别:
Regulation of Hippocampal Neurogenesis by Antidepressants
抗抑郁药对海马神经发生的调节
  • 批准号:
    7987729
  • 财政年份:
    2010
  • 资助金额:
    $ 39.32万
  • 项目类别:
Regulation of Hippocampal Neurogenesis by Antidepressants
抗抑郁药对海马神经发生的调节
  • 批准号:
    8267123
  • 财政年份:
    2010
  • 资助金额:
    $ 39.32万
  • 项目类别:

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