Evaluation of the effects of Thymus vulgaris essential oil in preventing morphine-induced tolerance and dependence in male mice

Abstract

Introduction: Previous research has demonstrated the roles of the glutamatergic system and oxidative stress in the development of morphine tolerance and dependence. Thymus vulgaris essential oil, due to its antioxidant properties and inhibitory effects on NMDA receptors, may effectively prevent morphine-induced tolerance and dependence.Aim: The aim of this study was evaluating the effects of intraperitoneal administration of Thymus vulgaris essential oil in preventing morphine-induced tolerance and dependence in male mice.Methods: Fifty male mice (20-30 grams) were randomly assigned to five groups of ten: a saline control group, a morphine control group, and three groups receiving Thymus vulgaris essential oil at doses of (25, 50, 100 mg/kg, i.p.). Treatments were administered daily for ten consecutive days. The essential oil was injected 30 minutes prior to the daily morphine injection. On day eleven, baseline measurements were taken, followed by the administration of morphine (9 mg/kg, i.p.) and the hot plate test was conducted within one hour. One hour after the hot plate test, naloxone (5 mg/kg, i.p.) was injected, and withdrawal symptoms were recorded for 30 minutes. The animals were then anesthetized, and blood samples were collected from the heart to measure serum levels of malondialdehyde (MDA) and total antioxidant capacity (TAC).Results: Administration of Thymus vulgaris essential oil at all doses (25, 50, 100 mg/kg, i.p.) significantly prevented morphine-induced tolerance and dependence (***P<0.001). The highest dose (100 mg/kg, i.p.) significantly decreased serum MDA levels (***P<0.001) and increased serum TAC levels (*P<0.05).Conclusion: The results suggest that Thymus vulgaris essential oil prevents morphine-induced tolerance and dependence, partially through its inhibitory effects on oxidative stress. Further studies are recommended to evaluate its potential in managing morphine-induced tolerance and dependence.