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The interaction between hippocampal GABA-B and cannabinoid receptors upon spatial change and object novelty discrimination memory function

Abstract

Rationale

Previous studies have postulated functional links between GABA and cannabinoid systems in the hippocampus. The aim of the present study was to investigate any possible interaction between these systems in spatial change and object novelty discrimination memory consolidation in the dorsal hippocampus (CA1 region) of NMRI mice.

Methods

Assessment of the spatial change and object novelty discrimination memory function was carried out in a non-associative task. The experiment comprised mice exposure to an open field containing five objects followed by the examination of their reactivity to object displacement (spatial change) and object substitution (object novelty) after three sessions of habituation.

Results

Our results showed that the post-training intraperitoneal administration of the higher dose of ACPA (0.02 mg/kg) impaired both spatial change and novelty discrimination memory functions. Meanwhile, the higher dose of GABA-B receptor agonist, baclofen, impaired the spatial change memory by itself. Moreover, the post-training intra-CA1 microinjection of a subthreshold dose of baclofen increased the ACPA effect on spatial change and novelty discrimination memory at a lower and higher dose, respectively. On the other hand, the lower and higher but not mid-level doses of GABA-B receptor antagonist, phaclofen, could reverse memory deficits induced by ACPA. However, phaclofen at its mid-level dose impaired the novelty discrimination memory and whereas the higher dose impaired the spatial change memory.

Conclusions

Based on our findings, GABA-B receptors in the CA1 region appear to modulate the ACPA-induced cannabinoid CB1 signaling upon spatial change and novelty discrimination memory functions.

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Acknowledgments

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

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Correspondence to Mohammad Nasehi or Mohammad-Reza Zarrindast.

Ethics declarations

All animal procedures were conducted in accordance with the institutional animal care as well as the NIH guidelines for ethics in animal research.

Additional information

Highlights

• Activation of CB1Rs impaired spatial change and object novelty discrimination memories.

• GABA-BR agonist or antagonist impaired spatial change or both memories, respectively.

• Subthreshold dose of baclofen restored ACPA response on both memories.

• Phaclofen dose-dependently restored both ACPA-induced memory deficits.

• An interaction between GABA-B and cannabinoid systems in the hippocampus was found.

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Nasehi, M., Alaghmandan-Motlagh, N., Ebrahimi-Ghiri, M. et al. The interaction between hippocampal GABA-B and cannabinoid receptors upon spatial change and object novelty discrimination memory function. Psychopharmacology 234, 3117–3128 (2017). https://doi.org/10.1007/s00213-017-4688-4

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  • DOI: https://doi.org/10.1007/s00213-017-4688-4

Keywords

  • CB1 receptors
  • GABA-B receptors
  • Spatial change memory
  • Object novelty discrimination memory
  • Mice