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The impact of chronic fentanyl administration on the cerebral cortex in mice: Molecular and histological effects

journal contribution
submitted on 2024-03-21, 08:35 and posted on 2024-03-21, 08:35 authored by Ayman Alzu'bi, Worood Bani Baker, Bahaa Al-Trad, Mazhar Salim Al Zoubi, Manal Isam AbuAlArjah, Ejlal Abu-El-Rub, Lena Tahat, Ahmed MNZ Helaly, Doaa S. Ghorab, Waseem El-Huneidi, Raed M. Al-Zoubi

Purpose

Fentanyl, a fully synthetic opioid, is widely used for severe pain management and has a huge abuse potential for its psychostimulant effects. Unlike other opioids, the neurotoxic effects of chronic fentanyl administration are still unclear. In particular, little is known about its effect on the cerebral cortex. The current study aims to test the chronic toxicity of fentanyl in the mice model.


Methods

Adult male Balb/c mice were chronically treated with low (0.05 mg/kg, i.p) and high (0.1 mg/kg, i.p) doses of fentanyl for 5 consecutive weeks, and various neurotoxic parameters, including apoptosis, oxidative stress, and neuroinflammatory response were assessed in the cortex. Potential histological as well as neurochemical changes were also evaluated.


Results

The results of this study show that chronic fentanyl administration induced intense levels of apoptosis, oxidative stress, and neuroinflammation in the cerebral cortex. These findings were found to be correlated with histopathological characteristics of neural degeneration and white matter injury. Moreover, fentanyl administration was found to reduce the expression of both NMDA receptor subunits and dopamine receptors and elevate the level of epidermal growth factor (EGF).


Conclusion

Fentanyl administration induced neurotoxic effects in the mouse cerebral cortex that could be primarily mediated by the evoked oxidative-inflammatory response. The altered expression of NMDA receptors, dopamine receptors, and EGF suggests the pernicious effects of fentanyl addiction that may end in the development of toxic psychosis.

Other Information

Published in: Brain Research Bulletin
License: http://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.1016/j.brainresbull.2024.110917

Funding

Open Access funding provided by the Qatar National Library.

History

Language

  • English

Publisher

Elsevier

Publication Year

  • 2024

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Medical Corporation
  • Qatar University
  • Qatar University Health - QU
  • College of Health Sciences - QU HEALTH

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