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Noradrenergic Regulation in the BNST

Noradrenergic Regulation in the BNST
BNST 中的去甲肾上腺素能调节
批准号:
9180250
负责人:
DANNY G WINDER
金额:
$35.29万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-07-01 至 2021-04-30

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中文摘要
翻译
项目摘要 上瘾给我们的社会带来了巨大的健康和经济负担。越来越多的文献表明 大脑中的去甲肾上腺素在压力-奖赏相互作用中起关键作用,这种相互作用可能调节关键的行为 对滥用药物的反应。一组以前未被认识的去甲肾上腺素能神经元 成瘾是通过腹侧去甲肾上腺素能束(VNAB)投射的细胞,被认为提供了关键 去甲肾上腺素。VNAB在大脑中的主要靶点是一组被称为扩展的 杏仁核。在之前的资助期间,我们确定了去甲肾上腺素能的每一主要类别的作用 终纹床核中兴奋性突触传递的受体,终纹的主要组成部分 延长的杏仁核。此外,我们还发现了一种新的机制,即去甲肾上腺素系统 与促肾上腺皮质激素释放因子受体信号系统相互作用以驱动特定的 VTA投射神经元的群体。我们还发现了α2-肾上腺素能受体的新作用。 对进入BNST的兴奋性驾驶的调节。 肾上腺素能配体已被确定为潜在的预防性治疗候选药物 上瘾。虽然人体研究的结果令人鼓舞,但他们在改善结果方面的总体成功 一直都很谦虚。我们认为,这部分是由于受体的许多不同的行为 受这些配体的调控,如果我们能更具体地理解 我们可以微调治疗策略,以增加 有效性。在这里,我们建议进行实验,以描绘儿茶酚胺- CRF信号相互作用调节应激诱导的可卡因寻求和α2-肾上腺素能受体诱导的可卡因寻找 抑制应力诱导的恢复。
英文摘要
Project Summary Addiction is a tremendous health and financial burden on our society. A growing literature indicates that norepinephrine in the brain plays a key role in stress-reward interactions that may mediate key behavioral responses to drugs of abuse. A previously unappreciated group of noradrenergic neurons in the field of addiction, cells that project through the ventral noradrenergic bundle (VNAB), are thought to supply the key norepinephrine. The primary target of the VNAB in the brain is a group of nuclei referred to as the extended amygdala. In the previous funding periods, we identified actions of each of the major classes of noradrenergic receptors on excitatory synaptic transmission in the bed nucleus of the stria terminalis, a major component of the extended amygdala. Moreover, we identified a novel mechanism whereby the noradrenergic system interacts with the corticotropin releasing factor receptor signaling system to drive recruitment of specific populations of VTA projecting neurons. We also identified novel actions of alpha2-adrenergic receptors in regulation of excitatory drive into the BNST. Adrenergic ligands have been identified as potential prophylactic therapeutic candidates in treating addiction. While results in human studies have been encouraging, their overall success in improving outcomes has been modest. We propose that this is in part due to the many disparate actions that the receptors regulated by these ligands regulate, and that if we could develop a more specific understanding of the regulated actions that were key to drug-seeking, we could fine tune treatment strategies to increase effectiveness. Here, we propose experiments to delineate specific pathways through which catecholamine- CRF signaling interactions regulate stress-induced cocaine seeking, and alpha2-adrenergic receptor-induced suppression of stress-induced reinstatement.
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Noradrenergic Regulation in the BNST
  • 批准号:
    9920688
  • 项目类别:
  • 资助金额:
    $35.27万
  • 财政年份:
    2016
  • 负责人:
    DANNY G WINDER
  • 依托单位:
Noradrenergic Regulation in the BNST
  • 批准号:
    10472646
  • 项目类别:
  • 资助金额:
    $40.71万
  • 财政年份:
    2016
  • 负责人:
    DANNY G WINDER
  • 依托单位:
Noradrenergic Regulation in the BNST
  • 批准号:
    9917488
  • 项目类别:
  • 资助金额:
    $4.14万
  • 财政年份:
    2016
  • 负责人:
    DANNY G WINDER
  • 依托单位:
Noradrenergic Regulation in the BNST
  • 批准号:
    9308915
  • 项目类别:
  • 资助金额:
    $35.28万
  • 财政年份:
    2016
  • 负责人:
    DANNY G WINDER
  • 依托单位:
海外基金