Cannabidiol promotes neurogenesis in the dentate gyrus during an abstinence period in rats following chronic exposure to methamphetamine

Abstract

Chronic methamphetamine (meth) abuse can lead to certain deficits in the hippocampal function by affecting the hippocampal neurogenesis and plasticity. To determine whether cannabidiol (CBD) can promote proliferation and maturation of neuronal progenitor cells, this study investigated the CBD effect on neurogenesis in the hippocampal dentate gyrus (DG) following chronic exposure to meth in rats. The rats received 2 mg/kg of meth twice a day for ten days. Next, immunofluorescence was performed to evaluate the effect of intracerebroventricular (ICV) administration of CBD (50 μg/5 μL) over an abstinence period (ten days) on the expression levels of neurogenesis markers, such as Ki67, NeuN, and doublecortin (DCX). Moreover, neuronal degeneration in the hippocampus was assessed using Nissl staining. According to our findings, repeated ICV administration of CBD improved cell proliferation and neurogenesis and increased the number of Ki-67 and DCX-positive cells in the abstinence period. Meanwhile, meth treatment subjects caused a significant decrease in the number of neurogenesis makers, as compared to the control group. The neurogenesis markers (Ki-67 and DCX) could be somewhat reversed, while NeuN did not show any significant increase in the CBD group. Our findings demonstrated that CBD can induce neuroprotective effects by modulating neurogenesis. Therefore, it can provide a promising therapeutic approach to improve cognitive performance following chronic exposure to psychostimulant drugs, including meth.

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Acknowledgements

This project was supported by the Vice-Chancellor for Research & Technology of Iran University of Medical Sciences (grant No. 95011127882) for funding this work. Also, the authors would like to thank the Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences.

Funding

Funding for this study was provided by the grant (No. 95111727882) from Vice-Chancellor for Research & Technology of Iran University of Medical Sciences, Tehran, Iran. The Vice-Chancellor for Research & Technology of Iran University of Medical Sciences had no further role in the design of the study; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

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Mehdi Mehdizadeh was responsible for the study concept and design. Yasaman Razavi contributed to the acquisition of data. Mehdi Mehdizadeh and Yasaman Razavi assisted with data analysis and interpretation of findings. Yasaman Razavi drafted the manuscript. Abbas Haghparast, Fariborz Keyhanfar and Ronak Shabani provided critical revision of the manuscript for important intellectual content. All authors critically reviewed content and approved final version for publication.

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Correspondence to Mehdi Mehdizadeh.

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All experiments were done in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No. 80–23, revised 1996) and were approved by the Research and Ethics Committee of Iran University of Medical Sciences, Tehran, Iran (IR.IUMS.REC1395.27882).

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Razavi, Y., Keyhanfar, F., Haghparast, A. et al. Cannabidiol promotes neurogenesis in the dentate gyrus during an abstinence period in rats following chronic exposure to methamphetamine. Metab Brain Dis 36, 1381–1390 (2021). https://doi.org/10.1007/s11011-021-00774-9

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Keywords

  • Neurogenesis
  • Methamphetamine
  • Cannabidiol
  • Chronic exposure
  • Abstinence
  • Dentate gyrus