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Subanesthetic ketamine exerts antidepressant-like effects in adult rats exposed to juvenile stress.

亚麻醉剂氯胺酮对暴露于幼年应激的成年大鼠发挥抗抑郁样作用。

  • 影响因子:3.15
  • DOI:10.1016/j.brainres.2020.146980
  • 作者列表:"Aikawa K","Yoshida T","Ohmura Y","Lyttle K","Yoshioka M","Morimoto Y
  • 发表时间:2020-06-13
Abstract

:Juvenile stress, like that caused by childhood maltreatment, is a significant risk factor for psychiatric disorders such as depression later in life. Recently, the antidepressant effect of ketamine, a noncompetitive N-methyl-d-aspartate receptor antagonist, has been widely investigated. However, little is known regarding its efficacy against depressive-like alterations caused by juvenile stress, which is clinically relevant in human depression. In the present study, we evaluated the antidepressant-like effect of ketamine in adult rats that had been subjected to juvenile stress. Depressive-like behavior was assessed using the forced swim test (FST), and electrophysiological and morphological alterations in the layer V pyramidal cells of the prelimbic cortex were examined using whole-cell patch-clamp recordings and subsequent recording-cell specific fluorescence imaging. We demonstrated that ketamine (10 mg/kg) attenuated the increased immobility time caused by juvenile stress in the FST, restored the diminished excitatory postsynaptic currents, and caused atrophic changes in the apical dendritic spines. Ketamine's effects reversing impaired excitatory/inhibitory ratio of postsynaptic currents were also revealed. These results indicated that ketamine could be effective in reversing the depression-like alterations caused by juvenile stress.

摘要

: 青少年压力,就像儿童期虐待引起的压力一样,是以后生活中抑郁症等精神疾病的重要危险因素。最近,非竞争性 N-甲基-d-天冬氨酸受体拮抗剂氯胺酮的抗抑郁作用已被广泛研究。然而,关于其对青少年应激引起的抑郁样改变的疗效知之甚少,这在人类抑郁症中具有临床意义。在本研究中,我们评价了氯胺酮在经历幼年应激的成年大鼠中的抗抑郁样作用。使用强迫游泳测试 (FST) 评估抑郁样行为,使用全细胞膜片钳记录和随后的记录细胞特异性荧光成像检查边缘前皮质 V 层锥体细胞的电生理和形态学改变。我们证明氯胺酮 (10 mg/kg) 减弱了 FST 中幼年应激引起的不动时间增加,恢复了兴奋性突触后电流减少,并引起了顶端树突棘的萎缩性变化。氯胺酮逆转突触后电流受损的兴奋性/抑制性比值的作用也被揭示。这些结果表明,氯胺酮可有效逆转青少年应激引起的抑郁样改变。

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影响因子:5.83
发表时间:2020-01-22
DOI:10.1523/JNEUROSCI.0786-19.2019
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影响因子:6.22
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DOI:10.1038/s41386-020-0614-2
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