Background and Aim : Administration of morphine (an important medicine) in the long run may cause tolerance to its pharmacological effects. Previous research has shown that the hydroalcoholic extract of Echinophora platyloba may inhibit the reinforcing effects of this drug in a conditioned place preference paradigm. This study aimed to evaluate the impact of the plant's hydroethanolic extract on the development of tolerance to morphine-induced hyperactivity induced by a high dose of this drug. Methods : In this study, 14 groups of male mice were randomly assigned to groups of eight. To assess the effects of drugs on locomotor activity, ten groups of the mice received saline and morphine (0.5-40 mg/kg, subcutaneously) or administered with the saline and the plant extract (25- 75 mg/kg, intraperitoneally). Moreover, during the morphine-induced hyperactivity tolerance induction phase, four groups of mice received either saline or the plant extract one hour prior to morphine. Results : While administration of high doses of morphine had a stimulatory effect on locomotor activity, the low doses of this drug decreased this behavior. Administration of all doses of the plant extract led to a decrease in spontaneous locomotor activity. Additionally, giving the plant extract prior to morphine during the tolerance induction phase diminished the development of tolerance to morphine-induced hyperactivity in the mice. Conclusion : The hydroethanolic extract of E. platyloba may offer protective effects against developing morphine tolerance. Therefore, it has the potential for further research as a drug in the treatment of morphine addiction.
