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Comparison between cannabidiol and sertraline for the modulation of post-traumatic stress disorder-like behaviors and fear memory in mice

Abstract

Rationale and objectives

Post-traumatic stress disorder (PTSD) is characterized by poor adaptation to a traumatic experience and disturbances in fear memory regulation, and currently lacks effective medication. Cannabidiol is a main constituent of Cannabis sativa; it has no psychotomimetic effects and has been implicated in modulating fear learning in mammals. Using a mouse PTSD model, we investigated the effects of CBD on PTSD-like behaviors and the modulation of trauma-related fear memory, a crucial process leading to core symptoms of PTSD.

Methods

We applied the modified pre-shock model to evaluated PTSD-like behaviors from days 3 to 26. The measures included the freezing time to the conditioned context, open field test, elevated plus maze test, and social interaction test. CBD and sertraline were administered at different stages of fear memory.

Results

CBD (10 mg/kg, i.p.) administration alleviated main PTSD-like symptoms in the mouse pre-shock model by attenuating trauma-related fear memory and anxiety-like behavior, and increasing social interaction behavior. The effects of CBD were apparent irrespective of whether it was administered before, during, or after re-exposure to the aversive context. However, sertraline (15 mg/kg, p.o.) was only effective when administered before the behavioral test. CBD also reduced the consolidation, retrieval, and reconsolidation of trauma-related fear memory, whereas sertraline only reduced fear-memory retrieval.

Conclusion

CBD produced anti-PTSD-like actions in mice and disrupted trauma-related fear memory by interfering with multiple aspects of fear memory processing. These findings indicate that CBD may be a promising candidate for treating PTSD.

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References

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Acknowledgements

We thank Drs. Yunfeng Li and Liming Zhang at the Beijing Institute of Pharmacology and Toxicology for their insightful discussions.

Funding

This work was supported by the Beijing Institute of Pharmacology and Toxicology.

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Authors and Affiliations

Authors

Contributions

X.H. and J.L. designed the experiments; N.W. and J.L. supervised the experiments; X.H., X.K.S., and K.D.S. performed the behavioral experiments; H.Y.G., X.K.S., K. D.S., B.G.X, and X.H analyzed the data and prepared the figures; and X.H. and N.W. wrote the paper with contributions from all the other coauthors.

Corresponding authors

Correspondence to Xiao Han or Ning Wu.

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Competing interests

The authors declare no competing interests.

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Xiao Han and Xiankui Song contributed equally.

This article belongs to a Special Issue on Cannabis and Cannabinoids.

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Han, X., Song, X., Song, D. et al. Comparison between cannabidiol and sertraline for the modulation of post-traumatic stress disorder-like behaviors and fear memory in mice. Psychopharmacology 239, 1605–1620 (2022). https://doi.org/10.1007/s00213-022-06132-6

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  • DOI: https://doi.org/10.1007/s00213-022-06132-6

Keywords

  • Post-traumatic stress disorder
  • Cannabidiol
  • Sertraline
  • Trauma-related fear memory processing
  • Endocannabinoid system