Differential mechanisms of opioidergic and dopaminergic systems of the ventral hippocampus (CA3) in anxiolytic-like behaviors induced by cholestasis in mice

There are several studies carried out to test the effect of cholestasis on memory impairment and anxiolytic-like behaviors. Some previous studies have shown that cholestasis alters the activity of opioidergic and dopaminergic systems. The aim of the present study is however to investigate the role of mu opioid, D1 and D2 dopamine ventral hippocampal (CA3) receptors upon cholestasis-induced anxiolytic-like behaviors in hole-board task. Male mice weighing 25-30 g were used. Cholestasis was induced by ligation of the main bile duct. Our data indicated that cholestasis can induce anxiolytic-like response. Furthermore, the results showed that the intra-CA3 injection of naloxone, a mu receptor antagonist at 0.25 and 0.5 µg/mouse, SCH23390, a D1 dopamine receptor antagonist or sulpiride, as a D2 dopamine receptor antagonist, 5 min before testing, reversed the cholestasis-induced anxiolytic-like behaviors seven days after bile duct ligation (BDL). Unlike the higher dose of SCH23390 (0.5 µg/mouse) which induced anxiogenic-like behaviors, other doses of the above drugs did not alter the exploratory behaviors in examined mice. Based on our findings, co-administration of the subthreshold dose of naloxone (0.125 µg/mouse), SCH23390 or sulpiride, and SCH23390 with sulpiride, neither altered exploratory behaviors in animals nor reversed the cholestasis-induced anxiolytic-like behaviors, seven days post BDL. Current results demonstrated firstly, the anxiolytic-like behaviors are evident in cholestatic mice seven days post BDL; secondly, there are plausible mechanisms governing the involvement of the CA3 opioidergic and dopaminergic systems in this phenomenon and thirdly, there seem to be no interaction between these systems.