| Introduction: Among various neurological systems involved in the development of morphine tolerance,
serotonergic and adrenergic systems are very significant. In this study, we used duloxetine to further
investigate the association between serotonergic and noradrenergic systems and the occurrence of
opioid tolerance. Materials and Methods: Six groups of male Wistar rats were studied including saline,
morphine, morphine + duloxetine (15, 30, and 60 mg.kg–1.day–1), and duloxetine-treated groups. Base
latency time (BL) was determined using hot plate test (50 ± 0.5ºC). The latency times were reported as
MPE% (maximum possible effect) and AUC (area under the curve) was calculated for each MPE%-Time
curve (to evaluate global analgesic effect). Results: Morphine-treated group showed tolerance on the 9th
day. As the same way, the groups treated with morphine and duloxetine (15, 30, 60 mg/kg) showed tolerance
on the 13th, 17th, and 23rd days, respectively. Duloxetine-treated group was tolerated on the 11th day.
There was a significant difference between the mean AUC in morphine + duloxetine (60 mg/kg-1/day–1) and
morphine-treated groups. Conclusion: Previous studies revealed that chronic administration of morphine
would reduce serotonin release in the central nervous system (CNS). This study showed the effective role
of duloxetine and the serotonergic system in postponing the tolerance to analgesic effects of morphine. |