The effect of Rosmarinic acid on occurrence of morphine withdrawal syndrome in mice

 Evidence indicates the beneficial effects of Lemon balm polyphenols in controlling morphine withdrawal syndrome. The effects of Rosmarinic acid, as one of the most active biological components of this plant, have not been studied in the field of opioid withdrawal syndrome, and therefore, this study was conducted with the aim of investigating the effect of Rosmarinic acid on this syndrome in an animal model. 

 To induce dependence, morphine was injected intraperitoneally three times a day (with doses of 50, 50, and 75 mg/kg respectively) for 3 days. On the fourth day after morphine, naloxone was administered to induce the withdrawal syndrome. Different doses of Rosmarinic acid (5, 10, and 20 mg/kg) as active treatments, clonidine, and saline (negative control) were injected in different and separate groups (n = 8), 30 minutes before naloxone. The levels of anxiety, irritability, and pain tolerance threshold were evaluated by elevated plus maze (EPM), open field, and hot plate tests after naloxone injection.

 Clonidine and Rosmarinic acid with a dose of 20 could significantly increase the presence of mice in the open arm of the EPM (p < 0.001). The excitability and motor activity in mice with withdrawal syndrome in the groups receiving 10 and 20 Rosmarinic acid and clonidine significantly decreased and the pain threshold increased (p < 0.05), and there was no significant difference between the Rosmarinic acid 20 and clonidine groups.

 These results clearly show that moderate to high doses of Rosmarinic acid (>10 mg/kg) are as effective as clonidine in suppressing the occurrence of morphine withdrawal syndrome and can be considered as a candidate in future clinical trials.