Antiamnesic effects of tofisopam against scopolamine-induced cognitive impairments in rats


Ucel U. I., CAN Ö. D., DEMİR ÖZKAY Ü., ULUPINAR E.

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, vol.190, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 190
  • Publication Date: 2020
  • Doi Number: 10.1016/j.pbb.2020.172858
  • Journal Name: PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Animal Behavior Abstracts, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Psycinfo, Veterinary Science Database
  • Keywords: Amnesia, GFAP, Ki-67, Rat, Synaptophysin, Tofisopam, ADULT HIPPOCAMPAL NEUROGENESIS, MORRIS WATER MAZE, DENTATE GYRUS, SYNAPTIC PLASTICITY, CELL-PROLIFERATION, MEMORY IMPAIRMENT, SPATIAL MEMORY, GRANULE CELLS, SYNAPTOPHYSIN, INHIBITION
  • Anadolu University Affiliated: Yes

Abstract

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.