Duloxetine attenuated morphine withdrawal syndrome in the rat

Long term exposure to morphine can induce dependence. The exact mechanisms of dependence are not yet fully understood. Many studies have been conducted to find new drugs that can prevent dependence. This study examined the effects of the chronic administration of duloxetine on the morphine withdrawal syndrome in rats.

To this end, male Wistar rats (170-220 g) were randomly divided into 5 groups including one saline treated group (non-depend­ent group) and 4 morphine dependent groups. The experimental groups received additive doses of morphine for 9 days in order to induce dependence according to the following protocol: day 1:5 mg/kg/12 h, days 2 and 3: 10 mg/kg/12 h, days 4, 5:15 mg/kg/12 h, days 6 and 7: 20 mg/kg/12 h and days 8 and 9: 25 mg/kg/12 h. On the ninth day, the morning dose of morphine was only injected. It is worth noting that 30 min before the morning dose of morphine, duloxetine (10, 20, and 40 mg/kg) was injected intraperitoneally. In addition, 2 h after the last injection of morphine, the morphine withdrawal was precipitated by naloxone. The withdrawal signs were recorded for 30 min; these signs included jumping, rearing, genital grooming, abdominal writhing, wet dog shaking, and teeth grinding.

The results of the study revealed that the chronic administration of duloxetine decreased all the withdrawal signs. Besides, it attenuated the total withdrawal scores significantly.

Results indicate that the regulatory effects on serotonergic and noradrenergic parameters might be associated with the amelioration of the withdrawal symptoms.