Objective: 

Alpha 2 (a2)-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 effects of dexmedetomidine and guanfacine (a2-adrenoceptor agonists) on morphine analgesia and tolerance in rats.

Methods: 

Adult male Wistar albino rats weighing 195–205 g were used in these experiments. 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 by the analgesia tests. The analgesic effects of dexmedetomidine (20 mg/kg), guanfacine (0.5 mg/kg), MK-467 (0,25 mg/kg; a2-adrenoceptor antagonist) and morphine were considered 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 significantly attenuated the expression of morphine tolerance (increased %MPE; p<0.05). On the contrary, the data suggested that MK-467 significantly decreased morphine analgesia in the tail-flick and hot-plate tests (decreased %MPE; p<0.05).

Conclusions: 

The interactions between noradrenergic and opioidergic mechanisms are complex. In addition, the localization of the receptor subtypes involved in the interactions of these systems with regard to antinociception and analgesic tolerance are still unclear. However, the obtained data suggested that the a2-adrenoceptor agonist dexmedetomidine and guanfacine increased antinociceptive effect of morphine and attenuated tolerance to morphine.