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.
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。