I.P. Pavlov Department of Physiology, Federal State Budget Scientific Institution "Institute of Experimental Medicine", St. Petersburg, Russia.
Psychopharmacology (Berl). 2022 Sep;239(9):2787-2798. doi: 10.1007/s00213-022-06159-9. Epub 2022 May 11.
Glibenclamide (GD) is a widely used medical drug; therefore, identifying the mechanisms underlying its pleiotropic effects in the central nervous system is urgent.
The aim of this work was to determine the ability of GD to modulate serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) transmission and to assess the dose-dependent effect of GD on cognitive function in rats during natural ageing.
In Experiment 1, rats received 10, 25, or 50 μg/kg GD intraperitoneally for 10 days. In Experiment 2, rats received 50 μg/kg GD intraperitoneally for 30 days. Spatial and working memory was assessed in the MWM and Y-maze tests, respectively. In both experiments, the levels of DA and 5-HT, their metabolites, and turnover rate were analysed by HPLC-ED in the rat hippocampus and striatum.
Changes in DA and 5-HT levels occurred only with a dose of 50 μg/kg GD. Therefore, in the second experiment, we administered a dose of 50 μg/kg GD. At this dose, GD prevented the development of impairments in spatial and working memory. The hippocampal concentrations of DA and DOPAC decreased, and the striatal concentrations of DA, DOPAC, 5-HT, and 5-HIAA increased.
One of the possible mechanisms of the precognitive effect of GD is its ability to modulate monoamine transmission. Thus, in translating our results to humans, GD can be recommended as a prophylactic agent for natural ageing to reduce the risk of developing cognitive impairments.
格列本脲（GD）是一种广泛使用的医学药物；因此，确定其在中枢神经系统中的多效作用的机制是当务之急。
本工作旨在确定 GD 调节 5-羟色胺（5-羟色胺，5-HT）和多巴胺（DA）传递的能力，并评估 GD 在自然衰老过程中对大鼠认知功能的剂量依赖性影响。
在实验 1 中，大鼠腹腔内给予 10、25 或 50μg/kg GD，共 10 天。在实验 2 中，大鼠腹腔内给予 50μg/kg GD，共 30 天。空间和工作记忆分别在 MWM 和 Y 迷宫测试中进行评估。在两个实验中，通过 HPLC-ED 在大鼠海马体和纹状体中分析 DA 和 5-HT 及其代谢物的水平及其周转率。
仅在 50μg/kg GD 剂量下才会发生 DA 和 5-HT 水平的变化。因此，在第二个实验中，我们给予 50μg/kg GD 的剂量。在该剂量下，GD 可预防空间和工作记忆障碍的发展。海马体中的 DA 和 DOPAC 浓度降低，纹状体中的 DA、DOPAC、5-HT 和 5-HIAA 浓度升高。
GD 具有预测作用的可能机制之一是其调节单胺传递的能力。因此，将我们的结果转化为人类时，可以推荐 GD 作为预防剂，用于自然衰老，以降低认知障碍的风险。
