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Interaction between NMDA and CB2 function in the dorsal hippocampus on memory consolidation impairment: an isobologram analysis

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Abstract

Rationale

Convincing evidence has supported the pivotal role of N-methyl-d-aspartate receptors (NMDARs) and CB2Rs in the regulation of learning and memory.

Objective

In this study, the role of hippocampal (CA1 region) CB2 receptors on aversive memory consolidation deficit induced by D-AP5, a NMDA receptor antagonist, was evaluated.

Methods

Adult male Wistar rats received cannula implants that bilaterally targeted the CA1 region. Long-term memory was examined using the step-through type of passive avoidance task.

Results

Post-training, intra-CA1 microinjection of D-AP5 (0.5 and 0.75 μg/rat), GP1a (CB2 receptor agonist at dose of 150 ng/rat) and AM630 (CB2 receptor antagonist at doses 75 and 100 ng/rat) impaired memory consolidation processes. Intra-CA1 microinjection of a lower dose of GP1a or AM630 restored memory impairment induced by D-AP5 at the two higher doses, while AM630 decreased D-AP5 memory response at the lower dose. The isobologram analysis showed that there is a synergistic effect between D-AP5 and AM630 on memory consolidation deficit.

Conclusions

These results suggest that CA1 CB2 receptors modulate memory consolidation impairment induced by D-AP5.

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Acknowledgements

Authors wish to thank the Iran National Science Foundation (INSF) for providing financial support to this project.

Author information

Authors and Affiliations

  1. Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences Branch, Islamic Azad University, P.O. Box 13145-784, Tehran, Iran

    Mohammad Nasehi & Mohammad-Reza Zarrindast

  2. Department of Pharmacology and Toxicology, Islamic Azad University, Pharmaceutical Science Branch (IAUPS), Tehran, Iran

    Marziyeh Hajikhani

  3. Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, Iran

    Mohaddeseh Ebrahimi-Ghiri

  4. Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran

    Mohammad-Reza Zarrindast

  5. Institute for Cognitive Science Studies (ICSS), Tehran, Iran

    Mohammad-Reza Zarrindast

  6. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad-Reza Zarrindast

  7. School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran

    Mohammad-Reza Zarrindast

  8. Medical Genomics Research Center, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran

    Mohammad-Reza Zarrindast

Authors
  1. Mohammad Nasehi
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  2. Marziyeh Hajikhani
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  3. Mohaddeseh Ebrahimi-Ghiri
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  4. Mohammad-Reza Zarrindast
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Corresponding authors

Correspondence to Mohammad Nasehi or Mohammad-Reza Zarrindast.

Additional information

Research highlights

• Intra-CA1 microinjection of D-AP5 impaired memory consolidation.

• Similar response was observed by activation or blockade of CB2Rs, dose-dependently.

• The lower dose of GP1a restored memory impairment induced by D-AP5.

• Subthreshold dose of AM630 modulated memory impairment induced by D-AP5.

• There is a synergistic effect between D-AP5 and AM630 on memory deficit.

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Nasehi, M., Hajikhani, M., Ebrahimi-Ghiri, M. et al. Interaction between NMDA and CB2 function in the dorsal hippocampus on memory consolidation impairment: an isobologram analysis. Psychopharmacology 234, 507–514 (2017). https://doi.org/10.1007/s00213-016-4481-9

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  • DOI: https://doi.org/10.1007/s00213-016-4481-9

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