| Background: Long term exposure to morphine
can induce dependence. The exact mechanisms
of dependence are not yet fully understood.
Many studies have been conducted to fi nd new
drugs that can prevent dependence. This study
examined the eff ects of the chronic administration
of duloxetine on the morphine withdrawal
syndrome in rats.
Methods: 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.
Results: The results of the study revealed that
the chronic administration of duloxetine decreased
all the withdrawal signs. Besides, it attenuated
the total withdrawal scores signifi cantly.
Conclusion: Results indicate that the regulatory
eff ects on serotonergic and noradrenergic
parameters might be associated with the amelioration
of the withdrawal symptoms. |