Department of Biology, Faculty of Basic Sciences, Tarbiat Moalem (Kharazmi) University, Tehran, Iran.
Arch Iran Med. 2012 Oct;15(10):617-24.
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.
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).
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.
It can be concluded that cholestasis differentially alters the reward effects of opioidergic and dopaminergic agents.
多项研究表明，在增加阿片类神经递质传递后，胆汁淤积会降低大脑中的阿片受体表达。阿片类系统在调节奖励回路中发挥着重要作用，而多巴胺依赖机制可能会产生这种作用。有人提出，伏隔核的多巴胺系统对于条件性位置偏爱（CPP）是必要的。因此，本研究旨在测试胆汁淤积是否会改变奖励系统以及阿片类和多巴胺系统在这一现象中的参与情况。
我们使用 CPP 和洞板范式分别测量小鼠的奖励效应和探索行为。通过使用两个结扎物结扎胆总管并在它们之间横断胆管来诱导胆汁淤积（BDL 小鼠）。
数据显示，吗啡（1 和 2 mg/kg）、舒必利（80 mg/kg）和 SKF38393（20 mg/kg）产生 CPP，而纳洛酮（1 mg/kg）和 SCH23390（1mg/kg）产生条件性位置厌恶（CPA），而喹吡罗对假手术组小鼠没有影响。然而，吗啡（2 mg/kg，ip）、舒必利（40 mg/kg）和 SKF38393（10 mg/kg）在 BDL 小鼠中诱导 CPP 与假手术组小鼠相比。与各自的假手术组小鼠相比，BDL 小鼠中纳洛酮或 SCH23390 诱导的 CPA 减少。喹吡罗在 BDL 小鼠中倾向于引起厌恶，但没有统计学意义。此外，喹吡罗（1 mg/kg）和 SCH23390（1 mg/kg）增加了头浸式探索行为，而纳洛酮（2 mg/kg）导致假手术组小鼠头浸式探索行为减少。吗啡（2 mg/kg）、SCH23390（1 mg/kg）和喹吡罗（0.25 和 0.5 mg/kg）在 BDL 小鼠中诱导焦虑样行为。
可以得出结论，胆汁淤积会改变阿片类和多巴胺类药物的奖励效果。
