Almasi-Nasrabadi Mina, Gharedaghi Mohammad Hadi, Rezazadeh Parisa, Dehpour Ahmad Reza, Javadi-Paydar Mehrak
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Pharmacol Biochem Behav. 2014 Nov;126:136-45. doi: 10.1016/j.pbb.2014.09.019. Epub 2014 Oct 2.
The present study has been undertaken to investigate the possible involvement of the glutamatergic pathway in the beneficial effects of pioglitazone on consolidation and retrieval phases of memory.
The Y-maze task was used to assess short-term spatial recognition memory in animals. Scopolamine (1mg/kg, i.p.) or MK-801 (dizocilpine) (0.03, 0.1 and 0.3mg/kg, i.p.) were administered immediately after the training session to impair memory consolidation or 30min before the retention trial to impair memory retrieval. Pioglitazone (10, 20, 40 and 80mg/kg, p.o.) was administered 2h before the retention session in memory retrieval experiments or immediately after the training session in consolidation experiments. And finally NMDA (N-methyl-d-aspartate) (75mg/kg, i.p) was administered 15min before the administration of pioglitazone.
Sub-effective dose of MK-801 is capable of reversing the protective action of pioglitazone on scopolamine-induced impairment of memory retrieval. Additionally, co-administration of 75mg/kg NMDA and a sub-effective dose of pioglitazone potentiated the effect of pioglitazone on memory retrieval impaired by scopolamine. These results support the idea that pioglitazone plays its memory retrieval enhancement role through the glutamatergic pathway.
本研究旨在探讨谷氨酸能通路是否参与吡格列酮对记忆巩固和提取阶段的有益作用。
采用Y迷宫任务评估动物的短期空间识别记忆。训练后立即腹腔注射东莨菪碱（1mg/kg）或MK-801（地佐环平）（0.03、0.1和0.3mg/kg）以损害记忆巩固，或在记忆提取试验前30分钟注射以损害记忆提取。在记忆提取实验中，于保留试验前2小时口服给予吡格列酮（10、20、40和80mg/kg）；在巩固实验中，于训练后立即给予。最后，在给予吡格列酮前15分钟腹腔注射NMDA（N-甲基-D-天冬氨酸）（75mg/kg）。
1）MK-801（0.3mg/kg）损害空间识别记忆的提取。2）吡格列酮未能改善MK-801诱导的空间识别记忆提取损害。3）20mg/kg剂量的吡格列酮显著改善了东莨菪碱诱导记忆提取损害小鼠的记忆。4）次有效剂量的MK-801（0.1mg/kg）能够逆转吡格列酮对东莨菪碱处理小鼠记忆提取的有益作用。5）给予NMDA（75mg/kg）和次有效剂量的吡格列酮（10mg/kg）可逆转东莨菪碱的作用并促进记忆提取。6）MK-801不影响空间识别记忆的巩固阶段。7）吡格列酮不影响东莨菪碱诱导的记忆巩固损害。
次有效剂量的MK-801能够逆转吡格列酮对东莨菪碱诱导的记忆提取损害的保护作用。此外，联合给予75mg/kg NMDA和次有效剂量的吡格列酮可增强吡格列酮对东莨菪碱损害的记忆提取的作用。这些结果支持吡格列酮通过谷氨酸能通路发挥其增强记忆提取作用的观点。
