Zwierzyńska Ewa, Andrzejczak Dariusz, Pietrzak Bogusława
Department of Pharmacodynamics, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, Poland.
Department of Pharmacodynamics, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, Poland.
Neurosci Lett. 2016 Jan 12;611:6-13. doi: 10.1016/j.neulet.2015.11.017. Epub 2015 Nov 17.
New antiepileptic drugs have been investigated for their potential role in the treatment of alcohol dependence. One of these drugs is retigabine and this study examines the effect of retigabine co-administered with ethanol on the development of alcohol dependence and the course of acute withdrawal syndrome. A pharmaco-EEG method was used to examine this impact in selected brain structures of rabbits (midbrain reticular formation, hippocampus and frontal cortex). Retigabine was administered p.o. at a dose of 5mg/kg/day with ethanol ad libitum for 6 weeks and then alone for 2 weeks during an abstinence period. Changes in bioelectric activity, which demonstrated the inhibitory effect of alcohol on the brain structures, were already visible after 2 weeks of ethanol administration. In the abstinence period, changes were of a different nature and significant neuronal hyperactivity was observed, particularly in the midbrain reticular formation and the hippocampus. This findings reveal that retigabine decreased ethanol-induced changes during both alcohol administration and abstinence periods. In particular, the modulatory effect of retigabine on the hippocampus may be a significant element of its mechanism of action in alcohol dependence therapy.
新型抗癫痫药物已被研究其在治疗酒精依赖方面的潜在作用。其中一种药物是瑞替加滨，本研究考察了瑞替加滨与乙醇联合使用对酒精依赖发展及急性戒断综合征病程的影响。采用药物脑电图方法在兔的特定脑结构（中脑网状结构、海马和额叶皮质）中检测这种影响。瑞替加滨经口给药，剂量为5mg/kg/天，与乙醇自由摄取共同给药6周，然后在戒断期单独给药2周。乙醇给药2周后，生物电活动的变化就已可见，这些变化表明酒精对脑结构具有抑制作用。在戒断期，变化性质不同，观察到明显的神经元活动亢进，特别是在中脑网状结构和海马。这些发现表明，瑞替加滨在酒精给药期和戒断期均能减轻乙醇诱导的变化。特别是，瑞替加滨对海马的调节作用可能是其在酒精依赖治疗中作用机制的一个重要因素。
