Nasehi Mohammad, Amin-Yavari Samaneh, Ebrahimi-Ghiri Mohaddeseh, Torabi-Nami Mohammad, Zarrindast Mohammad-Reza
Medical Genomics Research Center and School of Advanced Sciences in Medicine, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran.
Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Eur Neuropsychopharmacol. 2015 Apr;25(4):557-65. doi: 10.1016/j.euroneuro.2015.01.004. Epub 2015 Jan 16.
It is well documented that cannabinoids play an important role in certain hippocampal memory processes in rodents. On the other hand, N-Methyl-d-aspartate receptors (NMDARs) mediate the synaptic plasticity related to learning and memory processes which take place in the hippocampus. Such insights prompted us to investigate the influence of dorsal hippocampal (CA1) NMDA receptor agents on amnesia induced by cannabinoid CB1 receptor agonist, arachidonylcyclopropylamide (ACPA) in male mice. One-trial step-down passive avoidance and hole-board apparatuses were used to examine the memory retrieval and exploratory behaviors, respectively. Based on our findings, pre-training intraperitoneal (i.p.) administration of ACPA (0.01mg/kg) decreased memory acquisition. Moreover, pre-training intra-CA1 infusion of NMDA (0.001, 0.0125, 0.025 and 0.2µg/mouse), d-AP7 (0.5 and 1µg/mouse) or AM251 (50ng/mouse) impaired the memory acquisition. Meanwhile, NMDA-treated animals at the doses of 0.0005, 0.05 and 0.1µg/mouse acquired memory formation. In addition, intra-CA1 microinjection of NMDA (0.0005) plus different doses of ACPA potentiated the ACPA response, while NMDA (0.1) plus the lower or the higher dose of ACPA potentiated or restored the ACPA response, respectively. Further investigation revealed that a subthreshold dose of d-AP7 could potentiate the memory acquisition impairment induced by ACPA. Moreover, the subthreshold dose of AM251 did not alter the ACPA response, while the effective dose of the drug restored the memory acquisition impairment induced by ACPA. According to these results, we concluded that activation of the NMDA receptors in the CA1 mediates a dual effect on ACPA-induced amnesia in step-down passive avoidance learning task.
大量文献记载，大麻素在啮齿动物的某些海马记忆过程中发挥重要作用。另一方面，N-甲基-D-天冬氨酸受体（NMDARs）介导与海马体中发生的学习和记忆过程相关的突触可塑性。这些见解促使我们研究背侧海马体（CA1）NMDA受体药物对雄性小鼠中大麻素CB1受体激动剂花生四烯酰环丙酰胺（ACPA）诱导的失忆的影响。分别使用一次性降阶被动回避和洞板装置来检查记忆检索和探索行为。根据我们的研究结果，训练前腹腔注射（i.p.）ACPA（0.01mg/kg）会降低记忆获取。此外，训练前在CA1内注射NMDA（0.001、0.0125、0.025和0.2μg/小鼠）、d-AP7（0.5和1μg/小鼠）或AM251（50ng/小鼠）会损害记忆获取。同时，以0.0005、0.05和0.1μg/小鼠剂量的NMDA处理的动物获得了记忆形成。此外，在CA1内微量注射NMDA（0.0005）加不同剂量的ACPA增强了ACPA反应，而NMDA（0.1）加较低或较高剂量的ACPA分别增强或恢复了ACPA反应。进一步的研究表明，阈下剂量的d-AP7可以增强ACPA诱导的记忆获取损伤。此外，阈下剂量的AM251没有改变ACPA反应，而该药物的有效剂量恢复了ACPA诱导的记忆获取损伤。根据这些结果，我们得出结论，CA1中NMDA受体的激活在降阶被动回避学习任务中对ACPA诱导的失忆介导了双重作用。
