An Animal Model of a Behavioral Intervention for Depression
An Animal Model of a Behavioral Intervention for Depression
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DOI：
10.1016/j.neuron.2008.07.041
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发表时间：
2008-10-09
期刊：
影响因子：
16.2
通讯作者：
Kandell, Eric R.
中科院分区：
文献类型：
--
作者：
Pollak, Daniela D.;Monje, Francisco J.;Kandell, Eric R.
尽管恐惧的条件抑制（或习得性安全）是一种学习过程，对预防慢性压力至关重要，慢性压力是抑郁症和其他精神病理的诱发因素，但对其功能目的或分子机制知之甚少。为了更好地了解习得安全性，我们研究了它的行为和分子特征，发现它在两种动物模型中起行为抗抑郁药的作用。习得安全性促进海马齿状回新生细胞的存活，而其抗抑郁作用在海马神经发生切除的小鼠中被取消。习得性安全性还会增加海马中BDNF的表达，并导致参与杏仁核基底外侧多巴胺能和神经肽能系统的基因下调，但不涉及5 -羟色胺能系统。这些数据表明，习得安全性是一种行为抗抑郁药的动物模型，它具有一些药理抗抑郁药的神经元特征，但由不同的分子途径介导。
Although conditioned inhibition of fear (or learned safety) is a learning process critical for preventing chronic stress, a predisposing factor for depression and other psychopathologies, little is known about its functional purposes or molecular mechanisms. To obtain better insight into learned safety, we investigated its behavioral and molecular characteristics and found that it acts as a behavioral antidepressant in two animal models. Learned safety promotes the survival of newborn cells in the dentate gyrus of the hippocampus, while its antidepressant effect is abolished in mice with ablated hippocampal neurogenesis. Learned safety also increases the expression of BDNF in the hippocampus and leads to downregulation of genes involved in the dopaminergic and neuropeptidergic but not the serotonergic system in the basolateral amygdala. These data suggest that learned safety is an animal model of a behavioral antidepressant that shares some neuronal hallmarks of pharmacological antidepressants but is mediated by different molecular pathways.