The effect of quercetin (from onion) and ACTH on morphine induced tolerance and dependence in mice

The goal of this study was to evaluate the effects of ACTH and Quercetin on preventing the development of morphine tolerance and dependence in mice. In this study different groups of mice (20 30 g) received morphine (40 mg/kg, ip), morphine (40 mg/kg, ip) + ACTH (1,2.5,5 IU/mice, ip), morphine (40 mg/kg, ip) + Quercetin (5,10,25 mg/kg, ip), morphine (40 mg/kg, ip) + Quercetin (5mg/kg, ip)+ ACTH (1 IU/mice, ip)] once a day for four days. Tolerance was assessed by administration of morphine (9 mg/kg, ip) and using hot plate test on fifth day. Withdrawal symptoms were assessed by administration of naloxone (4 mg/kg, ip) two hours after co-administration of morphine with either Quercetin or ACTH. It was found that pretreatment with Quercetin or ACTH decreased the degree of tolerance and dependence significantly. Additionally, coadministration of Quercetin and ACTH before morphine administration decreased significantly the tolerance and dependencey. From these results it may be concluded that administration of Quercetin or ACTH injection alone or in together could affect the decrease withdrawal signs and tolerance of morphine. These effects may be related to as nitric oxide inhibitor (NOI) behavior of Quercetin and the ability of Morphine and their receptors in the control of the secretion of CRH. ACTH, quercetin and co-adminstration of both drugs significantly inhibited the development of morphine induced tolerance and dependence in mice.