Recent hypotheses propose that one prerequisite to obtain a rapid antidepressant (AD) effect would reside in processes of synaptic reinforcement occurring within the dentate gyrus (DG) of the hippocampus independently from neurogenesis. However, to date no relationship has been established between an increased DG synaptic plasticity, and rapid AD-like action. To the best of our knowledge, this study shows for the first time that inducing a long-term potentiation (LTP) within the DG by stimulating the perforant pathway (PP) is sufficient to induce such effects. Thus, Sprague-Dawley rats having undergone a successful LTP displayed a significant reduction of immobility when passed acutely 3 days thereafter in the forced swimming test (FST). Further, in a longitudinal paradigm using the pseudo-depressed Wistar-Kyoto rat strain, LTP elicited a decrease of FST immobility after only 2 days, whereas the AD desipramine was not effective before 16 days. In both models, the influence of LTP was transient, as it was no more observed after 8-9 days. No effects were observed on the locomotor activity or on anxiety-related behavior. Theta-burst stimulation of a brain region anatomically adjacent to the PP remained ineffective in the FST. Immunoreactivity of DG cells for phosphorylated histone H3 and doublecortin were not modified three days after LTP, indicating a lack of effect on both cell proliferation and neurogenesis. Finally, depleting brain serotonin contents reduced the success rate of LTP but did not affect its subsequent AD-like effects. These results confirm the 'plastic DG' theory of rapid AD efficacy. Beyond, they point out stimulations of the entorhinal cortex, from which the PP originates, as putative new approaches in AD research.

中文翻译：

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在齿状回中诱导长期增强足以产生快速的抗抑郁样作用。

最近的假设提出，获得快速抗抑郁（AD）效果的先决条件将在于海马齿状回（DG）发生的突触增强过程，而独立于神经发生。但是，迄今为止，在增加的DG突触可塑性和快速的AD样作用之间尚未建立任何关系。据我们所知，这项研究首次表明，通过刺激穿孔途径（PP）诱导DG内的长期增强（LTP）足以诱导此类效应。因此，经历了成功的LTP的Sprague-Dawley大鼠在强迫游泳试验（FST）之后3天急性通过时，其运动能力显着降低。此外，在使用伪压低的Wistar-Kyoto大鼠品系的纵向范例中，LTP仅在2天后引起FST固定性降低，而AD地昔帕明在16天前无效。在两个模型中，LTP的影响都是短暂的，因为在8-9天后不再观察到。没有观察到对运动活动或焦虑相关行为的影响。在FST中，解剖学上邻近PP的大脑区域的Theta-burst刺激仍然无效。LTP后三天未改变DG细胞对磷酸化组蛋白H3和双皮质素的免疫反应性，表明对细胞增殖和神经发生均缺乏影响。最后，耗尽脑中的血清素含量降低了LTP的成功率，但并未影响其随后的AD样效应。这些结果证实了快速AD功效的“塑料DG”理论。超过，