title: 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.
authors.affiliation: Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran. Electronic address: Nasehi@iricss.org.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Nasehi
authors.affiliation: Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mafi
authors.affiliation: Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, Iran.
authors.forename: Mohaddeseh
authors.initials: M
authors.lastname: Ebrahimi-Ghiri
authors.affiliation: Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran; School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran; Medical Genomics Research Center, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran; Institute for Cognitive Science Studies (ICSS), Tehran, Iran. Electronic address: zarinmr@ams.ac.ir.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000008:administration & dosage*; D005106:Exploratory Behavior / Q000187:drug effects*; D006501:Hepatic Encephalopathy / Q000503:physiopathology* / Q000523:psychology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D009270:Naloxone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D011954:Receptors, Dopamine / Q000502:physiology; D011957:Receptors, Opioid / Q000502:physiology; D013028:Space Perception / Q000187:drug effects*; D013469:Sulpiride / Q000008:administration & dosage
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D009292:Narcotic Antagonists; D011954:Receptors, Dopamine; D011957:Receptors, Opioid; C534628:SCH 23390; D009270:Naloxone; D013469:Sulpiride
keywords: Bile duct ligation; Dopamine; Opioid; Spatial and object novelty detection