Dextromethorphan attenuates and reverses analgesic tolerance to morphine

Area of Science:

• Pharmacology
• Neuroscience

Background:

• Morphine, a mu-opioid agonist, is a widely used analgesic.
• Development of tolerance to morphine's analgesic effects necessitates higher doses, increasing side effect risks.
• NMDA receptor antagonists have shown potential in modulating opioid tolerance.

Purpose of the Study:

• To investigate the effect of dextromethorphan on the development and reversal of morphine tolerance in male CD-1 mice.
• To determine if dextromethorphan can prevent or reverse the analgesic tolerance induced by morphine.

Main Methods:

• Morphine tolerance was induced in mice using escalating doses or sustained release pellets.
• Dextromethorphan was administered prior to or concurrently with morphine.
• Analgesic effects were assessed using the tail-flick test, and dose-response curves were analyzed to determine ED50 values.

Main Results:

• Dextromethorphan administration prevented a significant increase in morphine ED50 values during escalating dose and sustained release regimens.
• Concurrent administration of dextromethorphan via s.c. infusion also prevented a substantial increase in morphine ED50.
• Dextromethorphan treatment reversed established morphine tolerance, returning ED50 values close to baseline levels.

Conclusions:

• Dextromethorphan, an NMDA receptor antagonist, effectively modulates morphine-induced analgesic tolerance.
• These findings highlight a potential therapeutic strategy for managing opioid tolerance.