Acute hippocampal brain-derived neurotrophic factor restores motivational and forced swim performance after corticosterone.
Acute hippocampal brain-derived neurotrophic factor restores motivational and forced swim performance after corticosterone.
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DOI：
10.1016/j.biopsych.2008.06.016
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发表时间：
2008-11-15
影响因子：
10.6
通讯作者：
Taylor, Jane R.
中科院分区：
文献类型：
--
作者：
Gourley, Shannon L.;Kiraly, Drew D.;Howell, Jessica L.;Olausson, Peter;Taylor, Jane R.
细胞存活和可塑性的改变与抑郁症的神经生物学有关，这主要是基于对幼稚啮齿类动物抗抑郁疗效的表征，而不是基于捕获快感缺乏和动机丧失的衰弱和持久感觉的模型，这些是抑郁症的核心特征。在成年雄性小鼠中，我们评估了口服皮质酮（CORT）暴露对快感缺失样行为、强迫游泳试验（FST）中的不动性、渐进比例任务中的动机表现以及随后内源性CORT分泌的持续影响。在证实海马脑源性神经营养因子（BDNF）和cAMP反应元件结合蛋白磷酸化（pCREB）的长期降低后，研究了CORT暴露后直接海马BDNF微输注逆转缺陷的能力。先前的CORT暴露减少蔗糖消耗，食欲反应，和FST流动性没有长期影响水：奎宁歧视和内源性CORT分泌。重要的是，BDNF替代通过逆转CORT诱导的工具性能和FST移动性的降低来模拟慢性抗抑郁治疗（ADT）。总之，这些发现将海马BDNF表达和CREB转录活性的持续改变与持续的抑郁样状态联系起来，而不是ADT的疗效。这些结果确定海马BDNF作为双向调节食欲工具行为的重要分子底物。此外，我们认为这种CORT模型可能为未来研究复杂的压力相关抑郁症状的神经生物学提供了一个强大的工具，这些症状在压力暴露后持续很长时间。
Alterations in cellular survival and plasticity are implicated in the neurobiology of depression, based primarily on the characterization of antidepressant efficacy in naïve rodents, rather than on models that capture the debilitating and protracted feelings of anhedonia and loss of motivation that are core features of depression. In adult male mice, we evaluated persistent effects of oral corticosterone (CORT) exposure on anhedonic-like behavior, immobility in the forced swim test (FST), motivational performance in the progressive ratio task, and later endogenous CORT secretion. After verifying long-term decreases in hippocampal Brain-derived Neurotrophic Factor (BDNF) and cAMP Response Element Binding protein phosphorylation (pCREB), the ability of direct hippocampal BDNF microinfusion after CORT exposure to reverse deficits was investigated. Prior CORT exposure decreased sucrose consumption, appetitive responding, and FST mobility without long-term effects on water:quinine discrimination and endogenous CORT secretion. Critically, BDNF replacement mimicked chronic antidepressant treatment (ADT) by reversing CORT-induced reductions in instrumental performance and FST mobility. Together these findings link persistent alterations in hippocampal BDNF expression and CREB transcriptional activity with a persistent depressive-like state—as opposed to ADT efficacy. These results identify hippocampal BDNF as an essential molecular substrate that bidirectionally regulates appetitive instrumental behavior. Additionally, we suggest this CORT model may provide a powerful tool for future investigation into the neurobiology of complex stress-associated depressive symptoms that persist long after stress exposure itself.
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影响因子：
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