Objective: 

The efficacy of opioids is limited in chronic pain treatment, as a result of development of opioid tolerance. The aim of this study was to investigate the role of N-methyl-D-aspartate (NMDA) receptor antagonists on the morphine analgesia and tolerance in rats.

Methods: 

This study was applied on male Wistar albino rats (weighing 190±15 g). To constitute of morphine tolerance, animals received morphine (50 mg/kg; s.c.) once daily for 3 days. After last dose of morphine was injected on day 4, morphine tolerance was evaluated. The analgesic effects of ketamine, MK-801 (noncompetitive NMDA receptor antagonist), LY235959 (competitive NMDA receptor antagonist), cis-2,3-Piperidinedicarboxylic acid (PDA, NMDA receptor agonist), and morphine were considered at 30-min intervals (0, 30, 60, 90 and 120 min) by tail-flick and hot-plate analgesia tests (n=6 in each study group).

Results: 

The results demonstrated that ketamine, MK-801, and LY235959 significantly attenuated the development of morphine tolerance (p<0.05), on the other hand, PDA increased the development of morphine tolerance but, the difference was not statistically significant (p>0.05).

Conclusions: 

In conclusion, obtained data indicated that NMDA receptor antagonists attenuated the development of morphine tolerance and have a significant role on the morphine analgesia and tolerance in rats.