Piasecki J, Koros E, Dyr W, Kostowski W, Danysz W, Bienkowski P
Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.
Eur J Pharmacol. 1998 Aug 7;354(2-3):135-43. doi: 10.1016/s0014-2999(98)00442-7.
Ethanol has been reported to alter NMDA receptor-mediated biochemical and electrophysiological responses in vitro. The aim of the present study was to evaluate the effects of an uncompetitive NMDA receptor antagonist memantine, in animal models of alcoholism. Male Wistar rats were trained to drink 8% ethanol in a free-choice, limited access procedure. A separate group of animals was trained to lever press for 8% ethanol in an operant procedure where ethanol was introduced in the presence of sucrose. The selectivity of memantine's actions was assessed by studying its effects on food or water consumption in separate control experiments. Memantine (4.5-24 mg/kg) significantly, but not dose dependently, affected ethanol drinking in the limited access procedure. However, only 6 mg/kg memantine selectively decreased ethanol drinking. Memantine did not alter ethanol intake in rats trained to lever press for ethanol in the operant procedure. Only 9 mg/kg memantine reduced operant responding in the extinction procedure in the rats trained to lever press for ethanol. The same dose of memantine significantly reduced the operant behaviour of rats trained to respond for water. These results indicate that: (i) single doses of memantine only moderately and not dose dependently reduce alcohol drinking in the limited access procedure; (ii) memantine produces non-selective effects on operant behaviour in rats trained to lever press for ethanol in an oral self-administration procedure.
据报道，乙醇在体外可改变N-甲基-D-天冬氨酸（NMDA）受体介导的生化和电生理反应。本研究的目的是评估非竞争性NMDA受体拮抗剂美金刚在酒精中毒动物模型中的作用。雄性Wistar大鼠通过自由选择、限量摄入程序接受饮用8%乙醇的训练。另一组动物通过操作性程序接受按压杠杆获取8%乙醇的训练，在该程序中乙醇与蔗糖同时提供。在单独的对照实验中，通过研究美金刚对食物或水消耗的影响来评估其作用的选择性。美金刚（4.5 - 2 mg/kg）在限量摄入程序中显著影响乙醇饮用，但无剂量依赖性。然而，仅6 mg/kg美金刚选择性降低了乙醇饮用。美金刚在通过操作性程序接受按压杠杆获取乙醇训练的大鼠中未改变乙醇摄入量。仅9 mg/kg美金刚在接受按压杠杆获取乙醇训练的大鼠的消退程序中减少了操作性反应。相同剂量的美金刚显著降低了接受按压杠杆获取水训练的大鼠的操作性行为。这些结果表明：（i）单剂量美金刚在限量摄入程序中仅适度降低酒精饮用，且无剂量依赖性；（ii）美金刚在通过口服自我给药程序接受按压杠杆获取乙醇训练的大鼠中对操作性行为产生非选择性影响。
