Subanesthetic ketamine exerts antidepressant-like effects in adult rats exposed to juvenile stress
Subanesthetic ketamine exerts antidepressant-like effects in adult rats exposed to juvenile stress
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DOI：
10.1016/j.brainres.2020.146980
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发表时间：
2020-11-01
期刊：
影响因子：
2.9
通讯作者：
Morimoto, Yuji
中科院分区：
文献类型：
--
作者：
Aikawa, Katsuhiro;Yoshida, Takayuki;Morimoto, Yuji
青少年的压力，就像童年虐待造成的压力一样，是日后患上抑郁症等精神疾病的一个重要风险因素。氯胺酮是一种非竞争性的N-甲基-d-天冬氨酸受体拮抗剂，其抗抑郁作用近年来得到广泛研究。然而，关于其对青少年压力引起的抑郁样改变的疗效知之甚少，这与人类抑郁症临床相关。在本研究中，我们评估了氯胺酮的抗抑郁样作用，在成年大鼠已受到青少年的压力。抑郁样行为进行了评估，使用强迫游泳试验（FST），和电生理和形态学的改变，在第V层锥体细胞的前边缘皮层进行了检查，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。我们证明，氯胺酮（10毫克/公斤）衰减增加的不动时间所造成的幼年压力在FST，恢复减少兴奋性突触后电流，并引起萎缩性变化的顶端树突棘。氯胺酮的作用逆转受损的兴奋/抑制比突触后电流也被发现。这些结果表明，氯胺酮可以有效地逆转青少年应激引起的抑郁样改变。
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.