Single fluoxetine treatment before but not after stress prevents stress-induced hippocampal long-term depression and spatial memory retrieval impairment in rats.
Single fluoxetine treatment before but not after stress prevents stress-induced hippocampal long-term depression and spatial memory retrieval impairment in rats.
复制标题
在应激之前而不是应激之后进行单一氟西汀治疗可以预防应激引起的大鼠海马长期抑郁和空间记忆检索障碍。
DOI：
10.1038/srep12667
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发表时间：
2015-07-28
影响因子：
4.6
通讯作者：
Dong Z
中科院分区：
文献类型：
--
作者：
Han H;Dai C;Dong Z
越来越多的证据表明，长期服用氟西汀（一种广泛用于治疗抑郁症的处方药）会影响成人中枢神经系统的突触可塑性。然而，急性氟西汀是否会影响突触可塑性，特别是海马CA1长期抑制（LTD），以及如果会，是否会随后影响海马依赖的空间记忆，目前尚不清楚。在这里，我们报道了氟西汀（10mg /kg, i.p.）完全阻止了海马切片中平台升高应力导致的LTD。压力前30分钟。然而，应激后立即给予氟西汀并没有显著抑制LTD。同样，在电生理记录期间，氟西汀（10 μM）孵育对应力促进的LTD也没有影响。此外，行为学结果显示，急性应激前30分钟单次氟西汀治疗可完全逆转Morris水迷宫范式中空间记忆提取的损害。综上所述，仅在应激前而非应激后急性氟西汀治疗可预防成年动物行为应激引起的海马CA1 LTD和空间记忆恢复障碍。
A growing body of evidence has shown that chronic treatment with fluoxetine, a widely prescribed medication for treatment of depression, can affect synaptic plasticity in the adult central nervous system. However, it is not well understood whether acute fluoxetine influences synaptic plasticity, especially on hippocampal CA1 long-term depression (LTD), and if so, whether it subsequently impacts hippocampal-dependent spatial memory. Here, we reported that LTD facilitated by elevated-platform stress in hippocampal slices was completely prevented by fluoxetine administration (10 mg/kg, i.p.) 30 min before stress. The LTD was not, however, significantly inhibited by fluoxetine administration immediately after stress. Similarly, fluoxetine incubation (10 μM) during electrophysiological recordings also displayed no influence on the stress-facilitated LTD. In addition, behavioral results showed that a single fluoxetine treatment 30 min before but not after acute stress fully reversed the impairment of spatial memory retrieval in the Morris water maze paradigm. Taken together, these results suggest that acute fluoxetine treatment only before, but not after stress, can prevent hippocampal CA1 LTD and spatial memory retrieval impairment caused by behavioral stress in adult animals.