Department of Pharmacodynamics, Medical University of Lodz, Muszyńskiego 1, 90-151, Łódź, Poland.
Pharmacol Rep. 2021 Apr;73(2):480-489. doi: 10.1007/s43440-020-00205-z. Epub 2020 Dec 31.
Retigabine belongs to the novel generation of antiepileptic drugs but its complex mechanism of action causes that the drug might be effective in other diseases, for instance, alcohol dependence. It is known that ethanol abuse impaired the function of brain structures associated with memory and learning such as the hippocampus. In our previous study, retigabine reduced hippocampal changes induced by ethanol in the EEG rhythms in rabbits. This study is focused on the impact of retigabine on memory processes in male rats receiving alcohol.
Memory was evaluated in various experimental models: Morris water maze, Contextual, and Cued Fear Conditioning tests. Retigabine was administered for 3 weeks directly to the stomach via oral gavage at a dose of 10 mg/kg. Rats received also 20% ethanol (5 g/kg/day in two doses) via oral gavage for 3 weeks and had free access to 5% ethanol in the afternoon and at night. Morris water maze was performed after 1 and 3 weeks of ethanol administration and after 1 week from the discontinuation of ethanol administration. Contextual and Cued Fear Conditioning tests were carried out after 24 h and 72 h of alcohol discontinuation.
The drug significantly decreased ethanol-induced memory disturbances during alcohol administration as well as slightly improved learning processes after the discontinuation of ethanol administration.
This beneficial effect of retigabine-ethanol interaction on memory may be a relevant element of the drug's impact on the development of addiction.
瑞替加滨属于新型抗癫痫药物，但由于其作用机制复杂，可能对其他疾病有效，例如酒精依赖。已知乙醇滥用会损害与记忆和学习相关的大脑结构（如海马体）的功能。在我们之前的研究中，瑞替加滨减少了乙醇在兔脑电图节律中引起的海马变化。本研究侧重于瑞替加滨对接受酒精的雄性大鼠记忆过程的影响。
使用各种实验模型评估记忆：Morris 水迷宫、情境和线索恐惧条件反射测试。瑞替加滨通过口服灌胃以 10mg/kg 的剂量连续 3 周给药。大鼠也通过口服灌胃接受 20%乙醇（每天 5g/kg，分两次）连续 3 周，并在下午和晚上自由饮用 5%乙醇。在给予乙醇 1 周和 3 周后以及停止乙醇给予 1 周后进行 Morris 水迷宫测试。在停止酒精 24 小时和 72 小时后进行情境和线索恐惧条件反射测试。
该药物显著减少了乙醇给药期间引起的记忆障碍，并且在停止乙醇给药后略微改善了学习过程。
瑞替加滨-乙醇相互作用对记忆的这种有益影响可能是该药物对成瘾发展影响的一个相关因素。
