Evaluation of Bromocriptine effects in reversal morphine induced tolerance and dependence in mice

Abstract

Introduction: The main problem that follows the chronic use of opioids is the issue of dependence and tolerance, which occurs when morphine is stopped and symptoms of tolerance and morphine deprivation syndrome appear.In animals dependent on morphine, the functioning of the dopamine system decreases. Bromocriptine acts as an agonist of dopamine D2 receptors and increases dopamine.Aim: The aim of the present study was to evaluate the effects of subcutaneous administration of bromocriptine on morphine-induced tolerance and dependence in male rats.Methods: The studied animals were adult male mice in the weight range of 20-30 grams, which were divided into 5 groups of 10 including the saline control group, the control group (20% DMSO), and 3 groups receiving bromocriptine (0.04, 0.08, 0.16 mg/kg, s.c.). The injection of different doses of bromocriptine started from the eleventh day and half an hour before the daily injection of morphine was injected into the mice for four days. Then on the 15th day, after taking the base from the animals, morphine (9mg/kg, ip) was injected and the hot plate test was performed at 15, 30, 45, 60 minutes. Two hours after performing the hot plate test, naloxone (4mg/kg, ip) was injected and withdrawal symptoms (jumping and standing on two legs) were measured within half an hour. Finally, the animals were anesthetized by injecting ketamine and xylazine, and blood was drawn from the heart to measure the serum levels of MDA and TAC.Results: The results showed that the injection of bromocriptine (0.16 mg/kg, sc) in morphine-dependent animals reduces withdrawal symptoms in animals (p<0.01) .Conclusion: Based on these findings, the above-mentioned drug can be used to reduce the symptoms of morphine dependence. Bromocriptine, with the doses used in this study, may reduce dependence, except for the pathway of inhibiting oxidative stress.