Ondansetron and AS19 attenuate morphine tolerance by modulating serotonin 5-HT3 and 5-HT7 receptor expressions in rat dorsal root ganglia

Abstract

PurposeOpioid drugs are frequently preferred drugs for severe pain, but their long-term use causes tolerance to their analgesic effects. However, the factors that contribute to the development of tolerance to opioids are diverse and not fully understood. In this study, our aim was to investigate the effects of 5-HT3 receptor antagonist ondansetron (ODN) and 5-HT7 receptor agonist AS19 on morphine analgesia and tolerance in rats. Material and methodsEighty-four randomly selected Wistar Albino (230–260 g) male rats were included in the study. To induce morphine tolerance in rats, morphine (10 mg/kg) was administered subcutaneously twice daily for 7 days, and tolerance was assessed by thermal analgesia tests on day 8 for 120 min. After thermal analgesia tests, dorsal root ganglia (DRGs) at spinal L4-S5 level were isolated. 5-HT3 and 5-HT7 receptor expressions in DRGs were measured by immunohistochemical method. ResultsThe results show that co-administration of ODN or AS19 with morphine indicated a significant increase in analgesic effect compared to morphine alone In addition, the difference between the mean of ODN or AS19 combined with morphine and the morphine-tolerant group was statistically significant. H-score analysis significantly increased 5-HT3 receptor expressions in the morphine-tolerant rats, and administration of ODN prevented this. Similarly, 5-HT7 receptor expressions were significantly decreased in the morphine tolerant group, and the administration of AS19 increased this expression. ConclusionThese study results suggest that both ODN and AS19 alter the 5-HT3 and 5-HT7 receptor expressions in the DRG and possibly attenuate morphine tolerance in this way.