title: The effect of cholestasis on rewarding and exploratory behaviors induced by opioidergic and dopaminergic agents in mice.
abstract: BACKGROUND
  Several investigations have indicated that cholestasis decreases opioid receptor expression in the brain following increased opioidergic neurotransmission. The opioidergic system plays an important role in regulation of reward circuits that may be produced via dopamine-dependent mechanisms. It has been suggested that the dopaminergic system of the nucleus accumbens is necessary in conditioned place preference (CPP). The aim of this study is, therefore, to test if cholestasis can alter the reward system and the involvement of opioidergic and dopaminergic systems in this phenomenon.
  
  
  METHODS
  We used CPP and hole-board paradigms to measure the reward effect and exploratory behaviors, respectively, in mice. Cholestasis was induced by ligation of the main bile duct, using two ligatures and transecting the duct between them (BDL mice).
  
  
  RESULTS
  The data showed that morphine (1 and 2 mg/kg), sulpiride (80 mg/kg) and SKF38393 (20 mg/kg) produced CPP, while naloxone (1 mg/kg) and SCH23390 (1mg/kg) produced conditioned place aversion (CPA), whereas quinpirole had no effect in sham-operated mice. However, morphine (2 mg/kg, i.p.), sulpiride (40 mg/kg) and? SKF38393 (10 mg/kg) induced CPP in BDL mice compared to sham-operated mice. Naloxone- or SCH23390-induced CPA was reduced in BDL mice compared with the respective sham-operated mice. Quinpirole tended to induce aversion in BDL mice which was, however, not significant. In addition, quinpirole 1 mg/kg) and SCH23390 (1 mg/kg) increased head-dip exploratory behavior, whereas naloxone (2 mg/kg) caused a decrease in head-dip exploratory behavior in sham-operated mice. Morphine (2 mg/kg), SCH23390 (1 mg/kg) and quinpirole (0.25 and 0.5 mg/kg) induced anxiogenic-like behavior in BDL mice.
  
  
  CONCLUSIONS
  It can be concluded that cholestasis differentially alters the reward effects of opioidergic and dopaminergic agents.
authors.affiliation: Department of Biology, Faculty of Basic Sciences, Tarbiat Moalem (Kharazmi) University, Tehran, Iran.
authors.forename: Mohaddeseh
authors.initials: M
authors.lastname: Ebrahimi-ghiri
authors.forename: Mohammad
authors.initials: M
authors.lastname: Nasehi
authors.forename: Parvin
authors.initials: P
authors.lastname: Rostami
authors.forename: Homa
authors.initials: H
authors.lastname: Mohseni-Kouchesfehani
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D002779:Cholestasis / Q000503:physiopathology*; D015259:Dopamine Agents / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D012201:Reward; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D000701:Analgesics, Opioid; D001552:Benzazepines; D015259:Dopamine Agents; D009292:Narcotic Antagonists; C534628:SCH 23390; D019257:Quinpirole; D009270:Naloxone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D009020:Morphine; D013469:Sulpiride