Function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced in rodent model of hepatic encephalopathy

Abstract

Liver disease has been known for a long time to affect brain function. We now report the function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced by hepatic encephalopathy (HE) following bile duct ligation (BDL), a model of chronic liver disease. Assessment of spatial and object novelty detection memories was carried out in the non-associative task. It consists of placing mice in an open field containing five objects and, after three sessions of habituation, examining their reactivity to object displacement (spatial novelty) and object substitution (object novelty). Both spatial and object novelty detection memories were impaired by BDL after 4 weeks. In the BDL mice, pre-test intraperitoneal administration of naloxone (μ-opioidergic receptor antagonist) at dose of 0.9mg/kg restored while sulpiride (D2-like dopamine receptor antagonist) at dose of 40mg/kg potentiated object novelty detection memory deficit. However, SCH23390 (D1-like dopamine receptor antagonist) at dose of 0.04mg/kg or sulpiride (20mg/kg) restored spatial novelty detection memory deficit. Moreover, SCH23390 or sulpiride impaired while naloxone did not alter both memories in sham-operated mice. Furthermore, subthreshold dose co-administration of dopaminergic antagonists together or each one plus naloxone did not alter both memory impairments in BDL mice, while all of three co-administration groups impaired object novelty detection and co-administration of naloxone plus sulpiride impaired spatial detection memory in sham-operated mice. In conclusion, we suggest that opioidergic and dopaminergic systems through separate pathways may contribute in memory impairments induced by BDL in the non-associative task.

Bile duct ligation of C57BL/6 mice as a model of hepatic encephalopathy

“…Since BDL model has features of chronic liver disease and is technically relatively simple and quick to perform [ 13 , 14 ], it can be considered good experimental models for type C HE [ 3 ]. In fact, several studies have used BDL model in mice for HE research [ 6 – 11 ]. BDL in mice induces inflammatory liver injury and fibrosis through obstructive cholestasis [ 13 , 14 ].…”

“…Hepatotoxin models have been widely used to study HE caused by acute liver failure [ 3 – 5 ]. Meanwhile, for the research of HE in chronic liver disease, bile duct ligation (BDL) has been used [ 3 , 6 – 11 ]. BDL in rodents provides a model of secondary biliary fibrosis, which is characterized by proliferation of bile ductules, cholestasis, portal inflammation, and fibrosis [ 12 , 13 ].…”

“…BDL can be performed by double ligation of the common bile duct with or without transection at the midpoint between the two ligatures [ 6 – 11 , 13 , 14 ]. However, in the case of dissection of the bile duct between the ligatures, there is the risk of bile leaks if one knot is not secure, which results in severe peritonitis and mortality [ 14 ].…”

Interaction between hippocampal serotonin and cannabinoid systems in reactivity to spatial and object novelty detection

“…The apparatus used for the study was the same as in previous reports [30,31]. It was a metal circular box, 60 cm in diameter with a 20 cm-high wall.…”

Neurotransmitter mechanisms of paraphilic disorders

“…Так, например, агрессивное поведение у лиц с расстройствами влечений разного спектра в одном из исследований [12] тесно увязывается с активностью префронтальной коры и лимбической системы, а также с уровнем нейромодуляторов -дофамина, норэпинефрина, серотонина и опиатов. В другой работе [13] выявлены связи между активностью серотониновых рецепторов и орбитофронтальной корой: вследствие нарушения серотонинового контроля в этой области отмечается снижение критичности к расстройству и нарушается адекватное самовосприятие.…”