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Paper   IPM / Cognitive Sciences / 12826
School of Cognitive Sciences
  Title:   The effect of cholestasis on rewarding and exploratory behaviors induced by opioidergic and dopaminergic agents in mice
1.  Mohaddeseh Ebrahimi-ghiri
2.  Mohammad Nasehi
3.  Parvin Rostami
4.  Homa Mohseni-Kouchesfehani
5.  Mohammad Reza Zarrindast
  Status:   Published
  Journal: Arch Iran Med
  Vol.:  15
  Year:  2012
  Pages:   617-624
  Supported by:  IPM
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 signicant. 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. orphine (2 mg/kg), SCH23390 (1 mg/kg) and quinpirole (0.25 and 0.5 mg/kg) induced anxiogenic-like behavior in BDL mice. Conclusion: It can be concluded that cholestasis differentially alters the reward effects of opioidergic and dopaminergic agents.

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