Differential Effect of Chronic Morphine on Neuronal Degeneration in Male vs. Female Mice
Opioid abuse in the United States has been increasing at an alarming rate over the past 20 years. Sex differences are documented for the rates of opioid-related overdoses, abuse patterns, and drug-induced physiological effects. In our previous study, we demonstrated that chronic oxycodone administra...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | Pathophysiology |
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| Online Access: | https://www.mdpi.com/1873-149X/31/1/12 |
| _version_ | 1797239762006835200 |
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| author | Chet Brazile Ruping Fan Beau Benoit Thomas Arnold Nadejda Korneeva |
| author_facet | Chet Brazile Ruping Fan Beau Benoit Thomas Arnold Nadejda Korneeva |
| author_sort | Chet Brazile |
| collection | DOAJ |
| description | Opioid abuse in the United States has been increasing at an alarming rate over the past 20 years. Sex differences are documented for the rates of opioid-related overdoses, abuse patterns, and drug-induced physiological effects. In our previous study, we demonstrated that chronic oxycodone administration in young female rats is associated with neurodegeneration in the brain. Males and females are susceptible to neurodegenerative diseases via differing mechanisms. To investigate whether opioid exposure affects males and females differently, we treated young mice with chronic morphine. We observed that females had stronger antinociceptive responses to acute morphine and showed a delayed development of tolerance. Males had a higher basal Bax level in the brain that correlated with a higher number of apoptotic cells. Morphine increased Bax levels in both males and females without affecting the numbers of apoptotic cells. Morphine increased activated caspase 3 in axons and increased the MBP level in plasma only in females, suggesting a demyelination process. Our data suggest that males are protected from demyelination by having a higher basal BDNF level. Altogether, our results suggest that males and females have different molecular signaling underlying their patterns in the development of morphine tolerance and drug-induced neuronal degeneration. |
| first_indexed | 2024-04-24T17:56:41Z |
| format | Article |
| id | doaj.art-ef4548bc4a494954a251fddfcf73c0f7 |
| institution | Directory Open Access Journal |
| issn | 1873-149X |
| language | English |
| last_indexed | 2024-04-24T17:56:41Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathophysiology |
| spelling | doaj.art-ef4548bc4a494954a251fddfcf73c0f72024-03-27T13:59:03ZengMDPI AGPathophysiology1873-149X2024-03-0131115216510.3390/pathophysiology31010012Differential Effect of Chronic Morphine on Neuronal Degeneration in Male vs. Female MiceChet Brazile0Ruping Fan1Beau Benoit2Thomas Arnold3Nadejda Korneeva4School of Medicine, LSU Health Shreveport, Shreveport, LA 71103, USADepartment of Emergency Medicine, LSU Health Shreveport, Shreveport, LA 71103, USADepartment of Pharmacology, Toxicology and Neuroscience, LSU Health Shreveport, Shreveport, LA 71103, USADepartment of Emergency Medicine, LSU Health Shreveport, Shreveport, LA 71103, USADepartment of Emergency Medicine, LSU Health Shreveport, Shreveport, LA 71103, USAOpioid abuse in the United States has been increasing at an alarming rate over the past 20 years. Sex differences are documented for the rates of opioid-related overdoses, abuse patterns, and drug-induced physiological effects. In our previous study, we demonstrated that chronic oxycodone administration in young female rats is associated with neurodegeneration in the brain. Males and females are susceptible to neurodegenerative diseases via differing mechanisms. To investigate whether opioid exposure affects males and females differently, we treated young mice with chronic morphine. We observed that females had stronger antinociceptive responses to acute morphine and showed a delayed development of tolerance. Males had a higher basal Bax level in the brain that correlated with a higher number of apoptotic cells. Morphine increased Bax levels in both males and females without affecting the numbers of apoptotic cells. Morphine increased activated caspase 3 in axons and increased the MBP level in plasma only in females, suggesting a demyelination process. Our data suggest that males are protected from demyelination by having a higher basal BDNF level. Altogether, our results suggest that males and females have different molecular signaling underlying their patterns in the development of morphine tolerance and drug-induced neuronal degeneration.https://www.mdpi.com/1873-149X/31/1/12antinociceptiondemyelinationfemalemalemorphineneurodegeneration |
| spellingShingle | Chet Brazile Ruping Fan Beau Benoit Thomas Arnold Nadejda Korneeva Differential Effect of Chronic Morphine on Neuronal Degeneration in Male vs. Female Mice Pathophysiology antinociception demyelination female male morphine neurodegeneration |
| title | Differential Effect of Chronic Morphine on Neuronal Degeneration in Male vs. Female Mice |
| title_full | Differential Effect of Chronic Morphine on Neuronal Degeneration in Male vs. Female Mice |
| title_fullStr | Differential Effect of Chronic Morphine on Neuronal Degeneration in Male vs. Female Mice |
| title_full_unstemmed | Differential Effect of Chronic Morphine on Neuronal Degeneration in Male vs. Female Mice |
| title_short | Differential Effect of Chronic Morphine on Neuronal Degeneration in Male vs. Female Mice |
| title_sort | differential effect of chronic morphine on neuronal degeneration in male vs female mice |
| topic | antinociception demyelination female male morphine neurodegeneration |
| url | https://www.mdpi.com/1873-149X/31/1/12 |
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