Vocational School of Health Services, Bayburt University, Bayburt, Turkey.
Department of Pharmacology, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey.
Pharmacol Biochem Behav. 2020 Mar;190:172858. doi: 10.1016/j.pbb.2020.172858. Epub 2020 Jan 22.
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，我们研究了托非索泮（一种 2,3-苯并二氮杂䓬衍生物类抗焦虑药）对东莨菪碱诱导的健忘症大鼠认知功能障碍的潜在治疗作用。通过 Morris 水迷宫和被动回避测试来研究大鼠的认知性能。通过活动笼和转棒测试来评估运动活动的变化，然后通过免疫组织化学染色来评估海马体的形态变化。结果表明，东莨菪碱损害了大鼠的学习和记忆参数。认知表现恶化、神经元丢失以及海马突触素、Ki-67 和神经胶质纤维酸性蛋白密度降低。连续 7 天给予托非索泮 50mg/kg 剂量可改善受损的认知表现，增强海马突触传递的衰减，增加颗粒下层的增殖，并改善健忘症大鼠中星形胶质细胞的减少。这些发现首次指出了托非索泮的抗健忘作用，同时改善了海马体的突触发生、神经发生和神经胶质可塑性。鉴于 1,4-苯并二氮䓬类（经典抗焦虑药物）的最重要副作用之一是健忘症，托非索泮对认知功能障碍的有益影响具有显著的临床价值。然而，这些临床前结果需要首先通过进一步的临床研究来证实。
