Evaluating the effects of serteraline and bromocriptine on morphine induced dependence in male mice

Abstract

introduction: Despite the analgesic effects of morphine, it’s chronic use leads to tolerance and dependence studies indicate that serotonergic and dopaminergic system have important role on morphine induced dependence and withdrawal system. Bromocriptine acts as an agonist of dopamine D2 receptors, and sertraline increases serotonin by inhibiting serotonin reuptake Aim: evaluate possible role of D2 receptor and SSRIs on morphine induced dependence and withdrawal signs.Method: :10 groups of mice containing 9 male mouse (weighing 20-30 g) will randomly select and will give the following doses for 14 days. On the 11th day we will start to give medicine 30 minute before morphine injection. 1)Saline (10 ml/kg , ip) + Saline(10 ml/kg , ip) 2) Saline (10 ml/kg , ip) + Morphine(50 mg/kg , ip) 3)DMSO 20 % + morphine (50 mg/kg , ip) 4,5,6)Sertraline(5 , 10 , 20 mg/kg , ip) + Morphine(50mg/kg , ip) 7,8,9)Bromocriptine(0.04 , 0.08 , 0.16 mg/kg ,ip ) + Morphine(50 mg/kg , ip) 10)Sertraline (5mg/kg ,ip ) + Bromocriptine (0.04 mg/kg , ip ) + Morphine(50 mg/kg , ip) On the 14th day of administrating of morphine, 2 hour after the injection of the last morphine dose naloxone (5mg/kg , ip) will inject in all groups and sign of discontinuation (jumping and standing on both feet) will evaluate.Finally animals will be anesthetized by injection of ketamine (100 mg/kg , ip) and xylazine (10 mg/kg , ip). And blood samples will be taken from the heart to measure serum MDA and TAC levels.Result: Bromocriptine injection and co-injection of bromocriptine and sertraline reduced morphine dependence (p<0.01). And sertraline injection (20mg/kg, ip) caused a significant change in MDA and TAC levels (P<0.01).Conclusion:co-injection of bromocriptine and sertraline before the daily injection of morphine reduced morphine dependence