Acquisition and reinstatement of ethanol-induced conditioned place preference in rats: Effects of the cholinesterase inhibitors donepezil and rivastigmine
Acquisition and reinstatement of ethanol-induced conditioned place preference in rats: Effects of the cholinesterase inhibitors donepezil and rivastigmine
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DOI：
10.1177/0269881116642539
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发表时间：
2016-07-01
影响因子：
4.1
通讯作者：
Kotlinska, Jolanta H.
中科院分区：
文献类型：
--
作者：
Gawel, Kinga;Labuz, Krzysztof;Kotlinska, Jolanta H.
本研究观察了胆碱酯酶抑制剂多奈哌齐(乙酰胆碱酯酶选择性抑制剂)和利瓦斯明(丁酰胆碱酯酶抑制剂)对乙醇诱导的大鼠条件性位置偏爱(CPP)获得和恢复的影响。在CPP手术前，动物接受一次乙醇注射(0.5g/kg，10%w/v，腹腔注射)。已经15天了。采用四次注射乙醇(0.5g/kg，10%w/v，ip)建立小鼠酒精性CPP模型(偏心法)。每隔一天。对照组大鼠注射生理盐水，而不是乙醇。多奈哌齐(0.5、1或3 mg/kg，i.p)或利瓦斯明(0.03、0.5或1 mg/kg，i.p.)在乙醇诱导的CPP恢复之前或在乙醇诱导的CPP恢复之前给药。胆碱酯酶抑制剂在增加(剂量依赖的)乙醇诱导的CPP的获得方面同样有效。此外，预先注射两种抑制剂可恢复(交叉恢复)乙醇诱导的CPP，其效果相似。上述作用可被烟碱型乙酰胆碱受体拮抗剂甲乙酰胺(3 mg/kg，i.p.)所逆转，但不能被M胆碱型乙酰胆碱受体拮抗剂东莨菪碱(0.5 mg/kg，i.p.)所逆转。因此，我们的结果表明，胆碱能系统参与了乙醇的增强特性，烟碱型乙酰胆碱受体在复吸酒精的行为中发挥了重要作用。
The present study examined the influence of the cholinesterase inhibitors donepezil (a selective inhibitor of acetylcholinesterase) and rivastigmine (also an inhibitor of butyrylcholinesterase) on the acquisition and reinstatement of ethanol-induced conditioned place preference (CPP) in rats. Before the CPP procedure, animals received a single injection of ethanol (0.5 g/kg, 10% w/v, intraperitoneally [i.p.]) for 15 days. The ethanol-induced CPP (biased method) was developed by four injections of ethanol (0.5 g/kg, 10% w/v, i.p.) every second day. Control rats received saline instead of ethanol. Donepezil (0.5, 1 or 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5 or 1 mg/kg, i.p.) were administered before ethanol during conditioning or before the reinstatement of ethanol-induced CPP. The cholinesterase inhibitors were equally effective in increasing (dose dependently) the acquisition of ethanol-induced CPP. Furthermore, priming injections of both inhibitors reinstated (cross-reinstatement) the ethanol-induced CPP with similar efficacy. These effects of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist, but not by scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. Thus, our results show that the cholinergic system is involved in the reinforcing properties of ethanol, and nicotinic acetylcholine receptors play an important role in the relapse to ethanol-seeking behaviour.