Vascular endothelial growth factor signaling is required for the behavioral actions of antidepressant treatment: pharmacological and cellular characterization.
Vascular endothelial growth factor signaling is required for the behavioral actions of antidepressant treatment: pharmacological and cellular characterization.
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DOI：
10.1038/npp.2009.68
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发表时间：
2009-10
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影响因子：
--
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这项研究扩展了早期关于血管内皮生长因子（VEGF）在两个关键领域抗抑郁治疗作用的研究。首先，通过确定5-HT选择性再摄取抑制剂（SSRI），氟西汀在抑郁症/抗抑郁药反应的行为模型中的作用对VEGF的需求;其次，通过检查5-HT 1A受体亚型在VEGF调节中的作用，以及抗抑郁药调节VEGF表达的细胞定位。结果表明，VEGF受体信号传导的药理学抑制阻断了氟西汀在慢性不可预测应激大鼠中的行为作用。输注SU 5416或SU 1498（VEGF-Flk-1受体信号传导的两种结构不同的抑制剂）可阻断氟西汀对蔗糖偏好、强迫游泳试验中的不动性和新奇性抑制摄食范式中的摄食潜伏期的抗抑郁作用。我们还表明，5-HT 1A受体的激活足以诱导VEGF的表达，5-HT 1A拮抗剂阻断氟西汀诱导的VEGF和行为效应的增加。最后，双标记研究表明，氟西汀长期给药增加了海马神经元和内皮细胞的VEGF表达。总之，这些研究表明，VEGF是SSRI氟西汀以及去甲肾上腺素选择性再摄取抑制剂的行为效应所必需的，并且这些效应可能由位于神经元和内皮细胞上的5-HT 1A受体介导。
This study extends earlier work on the role of vascular endothelial growth factor (VEGF) in the actions of antidepressant treatment in two key areas. First, by determining the requirement for VEGF in the actions of a 5-HT selective reuptake inhibitor (SSRI), fluoxetine in behavioral models of depression/antidepressant response; and second, by examining the role of the 5-HT1A receptor subtype in the regulation of VEGF, and the cellular localization of antidepressant regulation of VEGF expression. The results show that pharmacological inhibition of VEGF receptor signaling blocks the behavioral actions of fluoxetine in rats subjected to chronic unpredictable stress. Infusions of SU5416 or SU1498, two structurally dissimilar inhibitors of VEGF–Flk-1 receptor signaling, block the antidepressant effects of fluoxetine on sucrose preference, immobility in the forced swim test, and latency to feed in the novelty suppressed feeding paradigm. We also show that activation of 5-HT1A receptors is sufficient to induce VEGF expression and that a 5-HT1A antagonist blocks both the increase in VEGF and behavioral effects induced by fluoxetine. Finally, double labeling studies show that chronic fluoxetine administration increases VEGF expression in both neurons and endothelial cells in the hippocampus. Taken together these studies show that VEGF is necessary for the behavioral effects of the SSRI fluoxetine, as well as norepinephrine selective reuptake inhibitor, and that these effects may be mediated by 5-HT1A receptors located on neurons and endothelial cells.
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影响因子：
6.9
作者：
Campbell, S;MacQueen, G
通讯作者：
MacQueen, G
影响因子：
7.6
作者：
Banasr, M;Hery, M;Daszuta, A
通讯作者：
Daszuta, A
DOI：
10.1073/pnas.0337481100
发表时间：
2003-02-04
影响因子：
11.1
作者：
MacQueen, GM;Campbell, S;Young, LT
通讯作者：
Young, LT
影响因子：
4.7
作者：
Mendez, J;Kadia, TM;Cowen, DS
通讯作者：
Cowen, DS
DOI：
10.1073/pnas.182296499
发表时间：
2002-09-03
影响因子：
11.1
作者：
Jin, KL;Zhu, YH;Greenberg, DA
通讯作者：
Greenberg, DA