Gawel Kinga, Labuz Krzysztof, Gibula-Bruzda Ewa, Jenda Malgorzata, Marszalek-Grabska Marta, Silberring Jerzy, Kotlinska Jolanta H
Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland.
Sahlgrenska University Hospital, Göteborg, Sweden.
J Psychopharmacol. 2016 Jul;30(7):676-87. doi: 10.1177/0269881116642539. Epub 2016 Apr 19.
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.
本研究考察了胆碱酯酶抑制剂多奈哌齐（一种乙酰胆碱酯酶的选择性抑制剂）和卡巴拉汀（也是丁酰胆碱酯酶的抑制剂）对大鼠乙醇诱导的条件性位置偏爱（CPP）的获得和恢复的影响。在进行CPP实验之前，动物连续15天每天接受一次乙醇注射（0.5 g/kg，10% w/v，腹腔注射[i.p.]）。乙醇诱导的CPP（偏差法）通过每隔一天注射四次乙醇（0.5 g/kg，10% w/v，腹腔注射）来建立。对照大鼠接受生理盐水而非乙醇。在条件训练期间乙醇注射前或乙醇诱导的CPP恢复前，给予多奈哌齐（0.5、1或3 mg/kg，腹腔注射）或卡巴拉汀（0.03、0.5或1 mg/kg，腹腔注射）。胆碱酯酶抑制剂在增加（剂量依赖性）乙醇诱导的CPP获得方面同样有效。此外，两种抑制剂的预注射都能以相似的效力恢复（交叉恢复）乙醇诱导的CPP。两种胆碱酯酶抑制剂的这些作用都被烟碱型乙酰胆碱受体拮抗剂美加明（3 mg/kg，腹腔注射）逆转，但未被毒蕈碱型乙酰胆碱受体拮抗剂东莨菪碱（0.5 mg/kg，腹腔注射）逆转。因此，我们的结果表明胆碱能系统参与了乙醇的强化特性，并且烟碱型乙酰胆碱受体在恢复觅酒行为中起重要作用。
