Abstract：
Post-traumatic stress disorder (PTSD) is associated with traumatic stress experiences. This condition can be accompanied by learning and cognitive deficits. Studies have demonstrated that ketamine can rapidly and significantly alleviate symptoms in patients with chronic PTSD. Nonetheless, the effects of ketamine on neurocognitive impairment and its mechanism of action in PTSD remain unclear.
In this study, different concentrations of ketamine (5, 10, 15, and 20 mg/kg, i.p.) were evaluated in rat models of single prolonged stress and electrophonic shock (SPS&S). Expression levels of brain-derived neurotrophic factor (BDNF) and post-synaptic density-95 (PSD-95) in the hippocampus (HIP) and amygdala (AMG) were determined by Western blot analysis and immunohistochemistry.
The data showed that rats subjected to SPS&S exhibited significant PTSD-like cognitive impairment. The effect of ketamine on SPS&S-induced neurocognitive function showed a U-shaped dose effect in rats. A single administration of ketamine at a dosage of 10-15 mg/kg resulted in significant changes in behavioral outcomes. These manifestations of improvement in cognitive function and molecular changes were reversed at high doses (15-20 mg/kg).
Overall, ketamine reversed SPS&S-induced fear and spatial memory impairment and the down-regulation of BDNF and BDNF-related PSD-95 signaling in the HIP and AMG. A dose equal to 15 mg/kg rapidly reversed the behavioral and molecular changes and promoted the amelioration of cognitive dysfunction. The enhanced association of BDNF signaling with PSD-95 effects could be involved in the therapeutic efficiency of ketamine for PTSD.
In this study, different concentrations of ketamine (5, 10, 15, and 20 mg/kg, i.p.) were evaluated in rat models of single prolonged stress and electrophonic shock (SPS&S). Expression levels of brain-derived neurotrophic factor (BDNF) and post-synaptic density-95 (PSD-95) in the hippocampus (HIP) and amygdala (AMG) were determined by Western blot analysis and immunohistochemistry.
The data showed that rats subjected to SPS&S exhibited significant PTSD-like cognitive impairment. The effect of ketamine on SPS&S-induced neurocognitive function showed a U-shaped dose effect in rats. A single administration of ketamine at a dosage of 10-15 mg/kg resulted in significant changes in behavioral outcomes. These manifestations of improvement in cognitive function and molecular changes were reversed at high doses (15-20 mg/kg).
Overall, ketamine reversed SPS&S-induced fear and spatial memory impairment and the down-regulation of BDNF and BDNF-related PSD-95 signaling in the HIP and AMG. A dose equal to 15 mg/kg rapidly reversed the behavioral and molecular changes and promoted the amelioration of cognitive dysfunction. The enhanced association of BDNF signaling with PSD-95 effects could be involved in the therapeutic efficiency of ketamine for PTSD.
摘要：
背景：创伤后应激障碍（PTSD）与创伤应激经历有关。这种情况可能伴随着学习和认知缺陷。研究表明，氯胺酮可以迅速，显着缓解慢性PTSD患者的症状。尽管如此，氯胺酮对PTSD神经认知障碍的影响及其作用机制尚不清楚。
方法：在本研究中，不同浓度的氯胺酮(5、10、15和20mg/kg，i.p.）在单次延长应激和电声休克（SPS＆S）的大鼠模型中进行评估。通过Westernblot分析和免疫组织化学检测海马（HIP）和杏仁核（AMG）中脑源性神经营养因子（BDNF）和突触后密度-95（PSD-95）的表达水平。
结果：数据显示，接受SPS&S的大鼠表现出明显的PTSD样认知障碍。氯胺酮对SPS&S诱导的大鼠神经认知功能的影响呈U型剂量效应。以10-15mg/kg的剂量单次施用氯胺酮导致行为结果的显著变化。认知功能改善和分子变化的这些表现在高剂量（15-20mg/kg）时被逆转。
结论：总体而言，氯胺酮逆转了SPS＆S诱导的恐惧和空间记忆障碍，以及HIP和AMG中BDNF和BDNF相关PSD-95信号的下调。等于15mg/kg的剂量迅速逆转了行为和分子的变化，并促进了认知功能障碍的改善。BDNF信号传导与PSD-95效应的增强关联可能涉及氯胺酮对PTSD的治疗效率。
方法：在本研究中，不同浓度的氯胺酮(5、10、15和20mg/kg，i.p.）在单次延长应激和电声休克（SPS＆S）的大鼠模型中进行评估。通过Westernblot分析和免疫组织化学检测海马（HIP）和杏仁核（AMG）中脑源性神经营养因子（BDNF）和突触后密度-95（PSD-95）的表达水平。
结果：数据显示，接受SPS&S的大鼠表现出明显的PTSD样认知障碍。氯胺酮对SPS&S诱导的大鼠神经认知功能的影响呈U型剂量效应。以10-15mg/kg的剂量单次施用氯胺酮导致行为结果的显著变化。认知功能改善和分子变化的这些表现在高剂量（15-20mg/kg）时被逆转。
结论：总体而言，氯胺酮逆转了SPS＆S诱导的恐惧和空间记忆障碍，以及HIP和AMG中BDNF和BDNF相关PSD-95信号的下调。等于15mg/kg的剂量迅速逆转了行为和分子的变化，并促进了认知功能障碍的改善。BDNF信号传导与PSD-95效应的增强关联可能涉及氯胺酮对PTSD的治疗效率。
