Brain Research ( IF 2.9 ) Pub Date : 2020-06-13 , DOI: 10.1016/j.brainres.2020.146980 Katsuhiro Aikawa 1 , Takayuki Yoshida 2 , Yu Ohmura 3 , Kerise Lyttle 3 , Mitsuhiro Yoshioka 3 , Yuji Morimoto 1
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.
中文翻译:
亚麻醉剂氯胺酮在暴露于青少年应激的成年大鼠中发挥抗抑郁样作用。
青少年压力,就像儿童期虐待造成的压力一样,是晚年精神疾病(如抑郁症)的重要危险因素。最近,氯胺酮的抗抑郁作用,一种非竞争性的N-甲基-d-天冬氨酸受体拮抗剂,已被广泛研究。然而,关于其对抗由青少年压力引起的抑郁样改变的功效知之甚少,这在临床上与人类抑郁症有关。在本研究中,我们评估了氯胺酮对遭受青少年应激的成年大鼠的抗抑郁作用。使用强迫游泳测试 (FST) 评估抑郁样行为,并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前边缘皮层 V 层锥体细胞的电生理学和形态学改变。我们证明氯胺酮 (10 mg/kg) 减弱了 FST 中由少年应激引起的不动时间增加,恢复了减弱的兴奋性突触后电流,并引起顶端树突棘的萎缩性改变。还揭示了氯胺酮逆转突触后电流的兴奋/抑制比受损的作用。这些结果表明氯胺酮可以有效逆转由青少年压力引起的抑郁样改变。