Low Dose Morphine Enhances Morphine Antinociception Effects in the Animals Pretreated with Selective and Non-Selective Phosphodiestrase Inhibitors

In this study, we investigated the interactive effects of intraperitoneal (i.p.)injections of three different phosphodiesterase inhibitors (pdeis) on morphineinducedanalgesia in mice using tail-flick method. subcutaneous administration ofmorphine (1, 3 and 6 mg/kg) caused significant antinociceptive effects in a dosedependent manner. administration of pentoxifylline (12.5, 25, 50 and 100 mg/kg,i.p.), milrinone (3 and 4.5 mg/kg, i.p.) and theophylline (25, 50 and 100 mg/kg, i.p.)as selective and non-seletive phosphodiesterase inhibitors induced analgesia inmice. we also examined the antinociceptive effects of these three pdeis incombination with non-effective dose of morphine (1 mg/kg). these combinationsincreased analgesia effects compared to the either morphine or respective phosphodiestraseinhibitor groups significantly. our findings strongly suggest that pdeiscan induce analgesia and potentiate morphine antinociception effect via possibleinteractions on the same molecular or biochemical pathways.