Evaluation the effect of bromocriptine and sulpiride on morphine dependence and withdrawal syndrome in mice

Several studies indicate that dopaminergic system has important role on morphine induced dependence and withdrawal syndrome.The aim of this study was to evaluate possible role of D2 receptor- by using bromocriptine and sulpiride (respectively agonist and antagonist of this receptor)- on morphine induced dependence and withdrawal signs. Experiments were performed on 17 groups (n=8) of adult male mice weighing between 20 and 25 g. Animals received saline (10 ml/kg, i.p.) or vehicle of drugs (DMSO 7% v/v + distilled water- 10 ml/kg, i.p.) or morphine (50 mg/kg, i.p.) or morphine with bromocriptine or sulpiride (10, 20, 40 mg/kg, i.p.) or morphine with both of drugs (bromocriptine and sulpiride). For evaluating of morphine dependence, animals received drugs one hour after morphine injection for six days. In order to assay of withdrawal symptoms drugs were injected only on the last day of morphine administration (6th day). For induction of withdrawal syndrome, naloxone (4 mg/kg, i.p.) was injected two hours after morphine injection on the last day and withdrawal signs (jumping and standing on feet) were evaluated for 30 minutes after naloxone injection. The results showed that bromocriptine has developed the morphine dependence and withdrawal syndrome significantly (p<0.05) but sulpiride only affected on number of standing on feet in dependence test study significantly (p<0.05) furthermore coadministration of bromocriptine and sulpiride could not affect on morphine dependence but increased the number of jumping in withdrawal syndrome study significantly (p<0.05). D2 receptors of dopaminergic system have a main role in morphine dependence and withdrawal syndrome but there are controversial results and the final effect of D2 agonists and antagonists administration remain to be elucidated.