The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling
The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling
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DOI：
10.1038/mp.2008.119
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发表时间：
2009-08-01
影响因子：
11
通讯作者：
Sousa, N.
中科院分区：
文献类型：
--
作者：
Bessa, J. M.;Ferreira, D.;Sousa, N.
抑郁症的发病/起始机制以及康复机制在很大程度上仍然未知；多年来，尽管最初的证据受到了质疑，但海马体中的神经发生可能对抑郁症症状的发病机制和改善具有重要作用的观点已经流行起来。在这项研究中，采用一种不可预测的慢性轻度应激方案在大鼠中诱导出类似抑郁的表型。在应激暴露的最后两周，动物接受抗抑郁药氟西汀、丙咪嗪、CP 156,526或SSR 149,415治疗，单独用药或与甲基氧化偶氮甲醇（一种用于抑制神经发生的细胞生长抑制剂）联合用药。我们发现，即使神经发生被阻断，抗抑郁药在降低所测量的类似抑郁行为的指标（习得性无助和快感缺失）方面仍然保持其治疗功效。相反，我们的实验表明，海马体和前额叶皮质中神经元可塑性（树突重塑和突触联系）的重建，而非神经发生，是抗抑郁药恢复行为稳态的基础。《分子精神病学》（2009年）14卷，764 - 773页；doi:10.1038/mp.2008.119；2008年11月4日在线发表
The mechanisms underlying the initiation/onset of, and the recovery from, depression are still largely unknown; views that neurogenesis in the hippocampus may be important for the pathogenesis and amelioration of depressive symptoms have gained currency over the years although the original evidence has been challenged. In this study, an unpredictable chronic mild stress protocol was used to induce a depressive-like phenotype in rats. In the last 2 weeks of stress exposure, animals were treated with the antidepressants fluoxetine, imipramine, CP 156,526 or SSR 1494515, alone or combined with methylazoxymethanol, a cytostatic agent used to arrest neurogenesis. We found that antidepressants retain their therapeutic efficacy in reducing both measured indices of depression-like behavior (learned helplessness and anhedonia), even when neurogenesis is blocked. Instead, our experiments suggest re-establishment of neuronal plasticity (dendritic remodeling and synaptic contacts) in the hippocampus and prefrontal cortex, rather than neurogenesis, as the basis for the restoration of behavioral homeostasis by antidepressants. Molecular Psychiatry (2009) 14, 764-773; doi:10.1038/mp.2008.119; published online 4 November 2008