The Role of Duloxetine in Changing the Process of Tolerance to Morphine Analgesic Effects in Male Rats

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.

Six groups of male Wistar rats were studied including saline, morphine, morphine + duloxetine (15, 30, and 60mg.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).

Morphine-treated group showed tolerance on the 9th day. As the same way, the groups treated with morphine and duloxetine (15, 30, 60mg/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 (60mg/kg-1/day–1) and morphine-treated groups.

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.