Effects of alpha 2-adrenoceptor agonists dexmedetomidine and guanfacine on morphine analgesia and tolerance in rats

BACKGROUND Alpha 2 (α(2))-adrenoceptor agonists may be useful for their potential to increase or prolong opioid analgesia while attenuating the development of opioid tolerance. The purpose of this study was to investigate the effects of dexmedetomidine and guanfacine (α(2)-adrenoceptor agonists) on morphine analgesia and tolerance in rats. METHODS Adult male Wistar albino rats weighing 195-205 g were used. To constitute morphine tolerance, animals received morphine (50 mg/kg) once daily for 3 days. After the last dose of morphine had been injected on day 4, morphine tolerance was evaluated by analgesia tests. The analgesic effects of dexmedetomidine (20 ug/kg), guanfacine (0.5 mg/kg), MK-467 (0.25 mg/kg), and morphine were estimated at 30-min intervals (0, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. RESULTS Our findings indicate that dexmedetomidine and guanfacine attenuated the expression of morphine tolerance. In addition, administration of dexmedetomidine with morphine increased morphine analgesia. On the contrary, data suggested that MK-467 (an α(2)-adrenoceptor antagonist) decreased morphine analgesia and increased morphine tolerance in analgesia tests. CONCLUSION In conclusion, we observed that co-injection of dexmedetomidine or guanfacine with morphine attenuated the expression of tolerance to the analgesic effect of morphine and that dexmedetomidine enhanced the morphine analgesia.