Pietrzak Bogusława, Czarnecka Elzbieta
Department of Pharmacodynamics, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, Poland.
Basic Clin Pharmacol Toxicol. 2006 Nov;99(5):383-90. doi: 10.1111/j.1742-7843.2006.pto_518.x.
The central effect of ethanol is mainly connected with the effect on GABAergic, glutamatergic, serotonergic and opioid transmission. The mechanism of gabapentin effect suggests that it may alleviate the rewarding effect of ethanol, which may be used in the treatment of addiction. We decided to examine the interaction of ethanol with gabapentin by a pharmaco-electroencephalographic (EEG) method. The influence of gabapentin on the effect of ethanol on EEG of rabbits (midbrain reticular formation, hippocampus, frontal cortex) was tested. Gabapentin was administered at a single dose (25 and 100 mg/kg orally) or repeatedly twice a day at a total dose of 25 mg/kg for 14 days. Ethanol was injected at a dose of 0.8 g/kg 60 min. after gabapentin treatment. Ethanol caused an increase in the slow frequencies (0.5-4 Hz) in the recording, as well as a marked decrease of the fastest frequencies (13-30 and 30-45 Hz). Gabapentin lead to changes in rabbit EEG recording suggesting an depressant effect on the CNS (increase of slow and decrease of fast frequencies). The effects were less pronounced after repeated doses, which may indicate adaptative changes in the receptors. Gabapentin administered both in a single dose and for 7 days markedly enhanced the effect of ethanol on EEG recordings in rabbits. Repeated doses of gabapentin decrease the sensitivity of the hippocampus to the effect of ethanol.
乙醇的中枢效应主要与对γ-氨基丁酸能、谷氨酸能、5-羟色胺能和阿片样物质传递的影响有关。加巴喷丁的作用机制表明,它可能减轻乙醇的奖赏效应,这可用于成瘾治疗。我们决定通过药物脑电图(EEG)方法研究乙醇与加巴喷丁的相互作用。测试了加巴喷丁对乙醇对兔脑电图(中脑网状结构、海马体、额叶皮质)影响的作用。加巴喷丁以单剂量(口服25和100mg/kg)给药,或每天两次重复给药,总剂量为25mg/kg,持续14天。在加巴喷丁治疗60分钟后,以0.8g/kg的剂量注射乙醇。乙醇导致记录中的低频(0.5 - 4Hz)增加,以及最快频率(13 - 30和30 - 45Hz)显著降低。加巴喷丁导致兔脑电图记录发生变化,表明对中枢神经系统有抑制作用(低频增加,高频降低)。重复给药后效果不太明显,这可能表明受体发生了适应性变化。单剂量和连续7天给药的加巴喷丁均显著增强了乙醇对兔脑电图记录的影响。重复给药的加巴喷丁降低了海马体对乙醇作用的敏感性。