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The Dual Effect of Ca1 Nmda Receptor Modulation on Acpa-Induced Amnesia in Step-Down Passive Avoidance Learning Task Publisher Pubmed



Nasehi M1 ; Aminyavari S2 ; Ebrahimighiri M3 ; Torabinami M4, 5 ; Zarrindast MR1, 6, 7, 8
Authors
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Authors Affiliations
  1. 1. Medical Genomics Research Center and School of Advanced Sciences in Medicine, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran
  2. 2. Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, Iran
  4. 4. Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
  5. 5. Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  6. 6. Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran

Source: European Neuropsychopharmacology Published:2015


Abstract

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 (0.01. mg/kg) decreased memory acquisition. Moreover, pre-training intra-CA1 infusion of NMDA (0.001, 0.0125, 0.025 and 0.2. μg/mouse), d-AP7 (0.5 and 1. μg/mouse) or AM251 (50. ng/mouse) impaired the memory acquisition. Meanwhile, NMDA-treated animals at the doses of 0.0005, 0.05 and 0.1. μg/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. © 2015 Elsevier B.V. and ECNP.
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