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

Abstract

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.

Protective effects of forced exercise against nicotine-induced anxiety, depression and cognition impairment in rat

“…On the other hand, our data indicate that bupropion (20 mg/kg), forced exercise, and forced exercise in combination with bupropion diminish depression-like behavior induced . Our results based on exercise are in accordance with the previous study, which indicates that physical activity can modulate depression and anxiety [15,17,24].…”

“…Upon the sudden discontinuation or attenuation of nicotine intake, a number of symptoms such as restlessness, anxiety, depression, and cognition impairment develop [1,21]. Previous studies have indicated that exercise lowers anxiety and stress levels and triggers the release of opioid-like peptides in the brain [15,22]. Physical activity can attenuate the severity of withdrawal symptoms by reducing depression and reducing anxiety and thereby facilitating the patient to regain a state of well-being [22,23].…”

“…Furthermore, physical activity and chronic forced exercise has been seen to induce anxiolytic-like effects in some experiments [15][16][17]. It has also been evident that exercise can reduce depression and increase cognitive functions [18].…”

“…Previous studies have demonstrated that exercise lowers stress and anxiety and increases the secretion of endorphin in the brain [15,16]. Furthermore, physical activity and chronic forced exercise has been seen to induce anxiolytic-like effects in some experiments [15][16][17].…”

Physiologic kinetic profile of glycemic response in a single dose of clonidine

“…[14] A 1 µg/kg clonidine premedication accentuated hyperglycemic responses to lower abdominal surgery caused by significant reduction in insulin plasma concentrations, [14] while an administration of 0.4 mg/kg clonidine significantly decreased glucose level. [18] The disagreement in the findings might be possibly due to the variations in the mode of administration (intraperitoneal vs. intravenous) and differences in stress conditions (surgery vs. no surgery). In this study, 1 µg/kg clonidine did not inhibit sympathoadrenergic stimulation suggesting changes in hypothalamic pituitary adrenal axis mainly regulate the serum glucose levels.…”