Evaluation of the effects of Carvacrol on Morphine induced tolerance and dependence in male mice

Abstract

Introduction: The mechanisms involved in the development of morphine tolerance and dependence include increased expression of P-glycoproteins and NMDA receptors, as well as activation of the oxidative stress system. Carvacrol, with its antioxidant effects, inhibition of P-gp gene expression, and NMDA receptor inhibition, appears to have beneficial effects in preventing morphine tolerance and dependence.Aim: To evaluate the effects of carvacrol on morphine-induced tolerance and dependence in male mice.Methods: Fifty male Swiss mice (weighing 20–30 grams, n=5) were randomly divided and subjected to the following regimens for 10 days: saline control group, morphine control group, and three groups receiving carvacrol (10, 20, 40 mg/kg). On the eleventh day, following the acquisition of base latency time from the animals, morphine (9 mg/kg, ip) was administered, and the hot plate test was conducted over one hour. One hour after the hot plate test, naloxone (4 mg/kg, ip) was injected, and withdrawal symptoms (jumping and rearing) were measured over 30 minutes. Blood samples were then collected, and the serum was separated for the determination of serum levels of MDA and TAC.Results: Administration of different doses of carvacrol (10, 20, 40 mg/kg, ip) did not cause significant changes in morphine tolerance reduction. However, administration of carvacrol (20, 40 mg/kg, ip) resulted in a significant decrease (**P<0.01) in morphine-induced dependence. Carvacrol (20, 40 mg/kg, ip) significantly decreased (***p<0.001) the serum MDA level, and carvacrol (40 mg/kg, ip) significantly increased (**p<0.01) the serum TAC level compared to the morphine control group. Conclusion: Carvacrol (20, 40 mg/kg, ip) prevents morphine dependence in animals, likely due to its beneficial mechanisms through the inhibition of the oxidative stress system.