Attenuation of morphine withdrawal signs, blood cortisol and glucose level with forced exercise in comparison with clonidine


1 Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

2 Department of Medical Biotechnology, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran


Background: Morphine withdrawal usually results in undesired outcomes , despite partial benefits of alternative medication such as methadone, because of the lack of mental sedation during the withdrawal period, may not lead to the desired result. In this study, forced exercise by treadmill is used to manage morphine dependence in animal model.
Materials and Methods: Forty adult male mice were divided into 5 groups, from which 4 groups became dependent by increasing daily doses of morphine for 6 days (20-45 mg/kg, SC). Afterwards, the animals were treated for 21 days by either of the following protocol: Positive control (dependent) received once daily 45 mg/kg of morphine sulfate (SC) for 21 day, group under treatment by clonidine (0.4 mg/kg, SC) for 21 day group under treatment by forced exercise by treadmill for 21 day, group under treatment by combination of clonidine (0.4 mg/kg, SC) and forced exercise by treadmill for 21day and the negative control group(independent) received saline injection like other groups. Each of this administration was injected at 8 AM. Finally, in the test day (day 28), all animals received a single dose of naloxone (3 mg/kg, SC) at 8 AM and then were observed for withdrawal signs, and Total Withdrawal Score (TWS) was determined as described previously. After withdrawal sign evaluation for evaluation of stress level of dependent mice, blood cortisol and glucose level were measured in non-fasting situations well.
Results: This study showed that TWS significantly decreased in all treatment groups in comparison with positive control group (P < 0.001). Moreover, blood cortisol and glucose level significantly decreased in group under treatment by clonidine (0.4 mg/kg) and group under treatment by combination of clonidine (0.4 mg/kg) and forced exercise by treadmill groups in comparison with control positive (dependent) (P < 0.05).
Conclusion: This study suggested that forced exercise can be useful as adjunct therapy in dependent people and can ameliorate side effects and stress situation of withdrawal syndrome periods.


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