The impact of chronic fentanyl administration on the cerebral cortex in mice: Molecular and histological effects
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Brain Research Bulletin |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923024000509 |
| _version_ | 1797256392414855168 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ayman Alzu'bi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T16:53:43Z |
| format | Article |
| id | doaj.art-0ffb790d775b4c1eada32b4dd907b77e |
| institution | Directory Open Access Journal |
| issn | 1873-2747 |
| language | English |
| last_indexed | 2024-04-24T22:21:01Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj.art-0ffb790d775b4c1eada32b4dd907b77e2024-03-20T06:08:32ZengElsevierBrain Research Bulletin1873-27472024-04-01209110917The impact of chronic fentanyl administration on the cerebral cortex in mice: Molecular and histological effectsAyman Alzu'bi0Worood Bani Baker1Bahaa Al-Trad2Mazhar Salim Al Zoubi3Manal Isam AbuAlArjah4Ejlal Abu-El-Rub5Lena Tahat6Ahmed MNZ Helaly7Doaa S. Ghorab8Waseem El-Huneidi9Raed M. Al-Zoubi10Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan; Corresponding author.Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan; Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid 211-63, JordanDepartment of Biological Sciences, Faculty of Science, Yarmouk University, Irbid 211-63, JordanDepartment of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, JordanDepartment of Biological Sciences, Faculty of Science, Yarmouk University, Irbid 211-63, JordanDepartment of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, JordanDepartment of Biological Sciences, Faculty of Science, Yarmouk University, Irbid 211-63, JordanDepartment of Clinical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan; Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, EgyptDepartment of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan; Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, EgyptDepartment of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, the United Arab EmiratesSurgical Research Section, Department of Surgery, Hamad Medical Corporation & Men‘s Health, Doha, Qatar; Department of Biomedical Sciences, QU-Health, College of Health Sciences, Qatar University, Doha 2713, Qatar; Department of Chemistry, Jordan University of Science and Technology, P.O.Box 3030, Irbid 22110, Jordan; Correspondence to: Surgical Research Section, Department of Surgery, Hamad Medical Corporation, Doha, Qatar.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.http://www.sciencedirect.com/science/article/pii/S0361923024000509FentanylNeurotoxicityOxidative StressNeuroinflammationApoptosis |
| spellingShingle | 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 The impact of chronic fentanyl administration on the cerebral cortex in mice: Molecular and histological effects Brain Research Bulletin Fentanyl Neurotoxicity Oxidative Stress Neuroinflammation Apoptosis |
| title | The impact of chronic fentanyl administration on the cerebral cortex in mice: Molecular and histological effects |
| title_full | The impact of chronic fentanyl administration on the cerebral cortex in mice: Molecular and histological effects |
| title_fullStr | The impact of chronic fentanyl administration on the cerebral cortex in mice: Molecular and histological effects |
| title_full_unstemmed | The impact of chronic fentanyl administration on the cerebral cortex in mice: Molecular and histological effects |
| title_short | The impact of chronic fentanyl administration on the cerebral cortex in mice: Molecular and histological effects |
| title_sort | impact of chronic fentanyl administration on the cerebral cortex in mice molecular and histological effects |
| topic | Fentanyl Neurotoxicity Oxidative Stress Neuroinflammation Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0361923024000509 |
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