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Bupropion attenuates morphine tolerance and dependence: Possible role of glutamate, norepinephrine, inflammation, and oxidative stress. | LitMetric

AI Article Synopsis

  • The study focuses on the issues of tolerance and dependence that arise from morphine use in pain management, highlighting the need for safer alternatives like bupropion, an antidepressant known for its excellent safety profile.* -
  • In an experiment with male Balb-c mice, researchers tested bupropion’s analgesic effects alongside morphine and found that, while bupropion didn’t enhance morphine's pain relief, it did reduce the development of morphine tolerance and dependence.* -
  • The findings suggest that bupropion could be an effective alternative to traditional treatments for mitigating morphine-related problems, without the same risks of dependency, making it a promising option in pain management.*

Article Abstract

Background: Morphine - the main pillar of nociceptive pain management - systemic use is associated with development of tolerance and dependence. Tolerance and dependence lay a heavy burden in clinical pain management settings. An added weight to this dilemma is that effective, safe, and tolerable solution to this problem is still beyond reach. Antidepressants were reported as possible alleviators of opioid tolerance and dependence. One of the increasingly used antidepressant in clinical practice is bupropion given its high safety and tolerability profile.

Methods: The study was performed on male Balb-c mice weighing 20-30g. Hot plate test was used for assessment of bupropion (5mg/kg, ip) possible analgesic activity and enhancement of morphine acute analgesia (1 and 5mg/kg, sc). Repeated morphine (5mg/kg, sc) administration for 9days developed tolerance and dependence, bupropion (5mg/kg, ip) was concurrently administered to evaluate its potential to modulate these processes. We also biochemically analyzed bupropion effect on these phenomena through modulation of neurotransmitters (glutamate and norepinephrine), inflammatory status (nitric oxide), and pro-antioxidant balance (malondialdehyde and reduced glutathione).

Results: Bupropion was devoid of intrinsic analgesic activity and did not enhance morphine acute analgesia. However, bupropion significantly attenuated morphine tolerance and dependence development and abstinence syndrome with corresponding suppression of morphine induced changes in glutamate, norepinephrine, inflammatory status, and prooxidant-antioxidant balance.

Conclusion: Bupropion efficacy in attenuation of morphine tolerance and dependence with its high safety and tolerability profile provide an alternative option to conventional agents e.g., ketamine and clonidine to modulate these phenomena.

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Source
http://dx.doi.org/10.1016/j.pharep.2018.04.003DOI Listing

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