THE EFFECT OF OPIOIDERGIC AGENTS ON DEPRESSION BEHAVIOR IN CHOLESTASIS AND ADDICTED MICE

Background and Aim : Depression is a mental illness frequently co-occurring with substance use. Addiction is a brain disorder characterized by compulsive engagement in rewarding stimuli despite adverse consequences. Cholestasis is a condition where bile cannot flow from the liver to the duodenum. An increase in the endogenous opioid peptide, met-enkephalin, has been reported during cholestatic liver disease and may be a predictor of reduced survival in patients with cholestasis. The effect of opioidergic agents (morphine and naloxone) on depression behavior in cholestasis and addicted mice was studied.Methods : There were four experimental groups: control, addicted, sham-operated and bile duct ligation (BDL) mice. Laparotomy was performed under general anesthesia induced by an intraperitoneal (i.p.) injection of ketamine hydrochloride (50 mg/kg) plus xylazine (5 mg/kg). The sham-operation consisted of a laparotomy and bile duct identification and manipulation without ligation or resection. In the BDL group, the main bile duct was first ligated using two ligatures approximately 0.5 cm apart and then transected at the midpoint between the two ligatures. In order to induction of addiction, the mice were treated with subcutaneous injections of morphine sulphate (25 mg/kg). These injections were given twice per day at 12 h intervals (06:00 and 18:00 h). Moreover, forced swim test (FST) was used to assess depression behavior in adult male mice. Results : Induction of experimental obstructive cholestasis and addiction changed depression behavior in mice. So, morphine increased immobility time in the FST [P < 0.05] compared to saline control group, indicating an antidepressant-like effect. On the other hand, naloxone reversed the response induced by morphine [P < 0.05]. Conclusion : The results show that opioid mechanism plays a role in modulation of depression behavior in experimental obstructive cholestasis and addicted mice.

کلیدواژه ها:

Addiction ، Cholestasis ، Morphine ، Naloxone ، Depression ، Mice