Synergistic effects between CA1 mu opioid and dopamine D1-like receptors in impaired passive avoidance performance induced by hepatic encephalopathy in mice

Background and aim

Numerous investigations have indicated that hepatic encephalopathy (HE) alters the levels of various neurotransmitters. However, comprehensive data regarding the effects of CA1 opioidergic and dopaminergic (DAergic) systems on HE-induced amnesia are still lacking.

Methods

Following intra-dorsal hippocampal (CA1) injection of mu opioid and dopamine D1- and D2-like receptors antagonists in male mice, one-trial step-down and hole-board paradigms were used to assess memory and exploratory behaviors, respectively.

Results

Our data demonstrated that HE impairs memory 24 days after bile duct ligation (BDL). Furthermore, while the higher dose of DA D1-like receptor antagonist (SCH23390, 0.5 μg/mouse) induced amnesia and anxiogenic-like behaviors, mu receptor antagonist (naloxone: 0.0125, 0.025 and 0.05 μg/mouse) and DA D2-like receptor antagonist (sulpiride: 0.0625, 0.125 and 0.25 μg/mouse) by themselves, could not exert an effect on memory performance in passive avoidance task. On the other hand, pre-test injection of all drugs reversed the HE-induced amnesia 24 days after BDL, while having no effect on exploratory behaviors. Pre-test co-administration of the subthreshold dose SCH23390 (0.25 μg/mouse) and sulpiride (0.0625 μg/mouse) or naloxone (0.0125 μg/mouse) could likewise reverse the BDL-induced amnesia. However, when the subthreshold sulpiride plus naloxone were co-administered, BDL-induced amnesia was not blocked.

Conclusions

Memory performance is impaired 24 days post BDL and CA1 mu opioid and DA D1-like receptors antagonist synergistic effects are likely involved in this phenomenon