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. 2011 Nov;116(4):238-46.
doi: 10.3109/03009734.2011.597889. Epub 2011 Sep 16.

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

Sinan Gursoy  1 , Ercan Ozdemir, Ihsan Bagcivan, Ahmet Altun, Nedim Durmus
Affiliations

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

Sinan Gursoy et al. Ups J Med Sci. 2011 Nov.

Abstract

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.

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Figures

Figure 1.
Figure 1.
Effects of dexmedetomidine (DEX; 20 μg/kg; i.p.) on morphine analgesia and tolerance in tail-flick (A) and hot-plate (B) tests. Each point represents the mean ± SEM of percent of maximal possible effect (% MPE) for 8 rats. *p < 0.05 compared to morphine group, **p < 0.01 compared to morphine-tolerant group.
Figure 2.
Figure 2.
Effects of guanfacine (0.5 mg/kg; i.p.) on morphine analgesia and tolerance in tail-flick (A) and hot-plate (B) tests. Each point represents the mean ± SEM of percent of maximal possible effect (% MPE) for 7 rats. *p < 0.01 compared to saline group, **p < 0.05 compared to morphine-tolerant group.
Figure 3.
Figure 3.
Effects of MK-467 (0.25 mg/kg; i.p.) on morphine analgesia and tolerance in tail-flick (A) and hot-plate (B) tests. Each point represents the mean ± SEM of percent of maximal possible effect (% MPE) for 7 rats. *p < 0.05 compared to MK-467 + morphine group, **p < 0.01 compared to MK-467 + morphine-tolerant group.
Figure 4.
Figure 4.
Analgesic effects of different doses of dexmedetomidine (5, 10, and 20 μg/kg; i.p.) as measured in tail-flick (A) and hot-plate (B) tests. Each point represents the mean ± SEM of percent of maximal possible effect (% MPE) for 8 rats. *p < 0.001, **p < 0.01 compared to saline-treated group.
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