Investigating the effects of tofisopam on cognitive parameters and hippocampal morphologies in rats with scopolamine induced amnesia

In this thesis study, therapeutic potential of tofisopam, a 2,3-benzodiazepine derivative anxiolytic drug, in the treatment of cognitive disorders, were investigated by using rats with scopolamine induced amnesia. The cognitive performances of the rats were assessed by Morris water maze and passive avoidance methods; alterations in the motor activites were investigated by activity cage and Rota-rod tests, and morphological changes in hippocampus were evaluated by various immunohistochemical methods. Obtained findings indicate that scopolamine administration significantly impairs the learning and memory parameters of rats. The failing of the cognitive performance was accompanied by decreased hippocampal synaptophysin, Ki-67 and GFAP densities, and sudden neuronal loss. Administration of tofisopam at a dose of 50 mg/kg for 7 days increased the impaired cognitive performance of amnesic rats; reinforced the weakened hippocampal synaptic transmission, increased proliferation in the subgranular areas, and improved the astroglial retraction, significantly. The anti-amnesic efficacy potential of tofisopam as well as its beneficial effects on hippocampal synaptogenesis, neurogenesis and glial plasticity were demonstrated for the first time, in this study. Considering that one of the most important side effects of the classical 1,4-benzodiazepines is amnesia, the importance of beneficial effect of anxiolytic drug, tofisopam, on cognitive functions can be better understood clinically. On the other hand, the anti-amnestic activity potential of tofisopam demonstrated by this preclinical study needs to be confirmed by well-designed clinical trials.