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NG-nitro-L-arginine prevents morphine tolerance
Y A Kolesnikov1, C G Pick, G W Pasternak
1Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
European Journal of Pharmacology
|October 20, 1992
Summary
Nitric oxide synthase inhibitors, like NG-nitro-L-arginine, prevent morphine tolerance by blocking NMDA receptor activation. This finding suggests nitric oxide plays a key role in opioid tolerance development.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Opioid analgesics, such as morphine, are widely used for pain management.
- Development of tolerance to morphine limits its long-term efficacy.
- NMDA receptor antagonists are known to prevent morphine tolerance.
Purpose of the Study:
- To investigate the role of nitric oxide in the development of morphine tolerance.
- To determine if inhibiting nitric oxide synthase affects morphine tolerance.
Main Methods:
- Morphine tolerance was induced in animals through daily administration.
- The effect of co-administering NG-nitro-L-arginine (a nitric oxide synthase inhibitor) with morphine was assessed.
- Analgesic responses to morphine were measured over time.
Main Results:
- Daily morphine administration led to a rapid decrease in analgesic response (tolerance) within 5 days.
- Coadministration of NG-nitro-L-arginine with morphine significantly prevented the development of tolerance for at least 11 days.
- The analgesic effect of morphine was maintained for a longer duration when nitric oxide synthase was inhibited.
Conclusions:
- Morphine tolerance appears to involve the activation of NMDA receptors.
- The subsequent release of nitric oxide is implicated in the mechanism of morphine tolerance.
- Inhibiting nitric oxide synthase offers a potential strategy to mitigate opioid tolerance.