In this study, we investigated the potential therapeutic effects of tofisopam, a 2,3-benzodiazepine derivative anxiolytic, on cognitive deficits in rats with scopolamine-induced amnesia. Cognitive performance of the rats was investigated by using the Morris water maze and passive avoidance tests. Changes in motor activity were assessed by using the activity cage and Rota-rod tests and then morphological changes in the hippocampus were assessed via immunohistochemical stainings. The results indicated that scopolamine impaired learning and memory parameters in rats. Worsened cognitive performance, neuronal loss, and decreased hippocampal synaptophysin, Ki-67, and glial fibrillary acidic protein density were observed. Tofisopam administration at a dose of 50 mg/kg for seven days improved the impaired cognitive performance, enhanced the attenuated synaptic transmission in the hippocampus, increased proliferation in subgranular zones, and improved the decrease in astrocytes in amnesic rats. These findings point out the anti-amnesic effects of tofisopam with concomitant improvements in the hippocampal synaptogenesis, neurogenesis, and glial plasticity, for the first time. Presented beneficial effects of tofisopam on cognitive dysfunctions may have a notable clinical value considering the fact that one of the most important side effects of 1,4-benzodiazepines, which are classical anxiolytic drugs, is amnesia. However, these preclinical results need to be confirmed with further clinical studies, first.

在这项研究中，我们调查了2，3-苯并二氮杂卓衍生物托非索坦对东pol碱引起的失忆症大鼠认知功能障碍的潜在治疗作用。通过使用莫里斯水迷宫和被动回避测试研究了大鼠的认知能力。通过使用活动笼和Rota-rod测试评估运动活动的变化，然后通过免疫组织化学染色评估海马的形态变化。结果表明东碱损害大鼠的学习和记忆参数。观察到认知能力恶化，神经元丧失，海马突触素，Ki-67和神经胶质纤维酸性蛋白密度降低。以50 mg / kg的剂量服用Tofisopam 7天可改善认知功能受损，增强健忘大鼠海马突触传递的减弱，增加颗粒下区域的增殖，并改善星形胶质细胞的减少。这些发现首次指出了托非索坦的抗遗忘作用以及海马突触形成，神经发生和神经胶质可塑性的同时改善。考虑到作为经典抗焦虑药的1,4-苯二氮卓类药物最重要的副作用之一是健忘症这一事实，托非索坦对认知功能障碍的有益作用可能具有显着的临床价值。但是，这些临床前结果首先需要进一步的临床研究来证实。这些发现首次指出了托非索坦的抗遗忘作用以及海马突触形成，神经发生和神经胶质可塑性的同时改善。考虑到作为经典抗焦虑药的1,4-苯二氮卓类药物最重要的副作用之一是健忘症这一事实，托非索坦对认知功能障碍的有益作用可能具有显着的临床价值。但是，这些临床前结果首先需要进一步的临床研究来证实。这些发现首次指出了托非索坦的抗遗忘作用以及海马突触形成，神经发生和神经胶质可塑性的同时改善。考虑到作为经典抗焦虑药的1,4-苯二氮卓类药物最重要的副作用之一是健忘症这一事实，托非索坦对认知功能障碍的有益作用可能具有显着的临床价值。但是，这些临床前结果首先需要进一步的临床研究来证实。传统的抗焦虑药4-苯二氮卓为健忘症。但是，这些临床前结果首先需要进一步的临床研究来证实。传统的抗焦虑药4-苯二氮卓为健忘症。但是，这些临床前结果首先需要进一步的临床研究来证实。