Abstract

BackgroundRetigabine 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.MethodsMemory 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.ResultsThe drug significantly decreased ethanol-induced memory disturbances during alcohol administration as well as slightly improved learning processes after the discontinuation of ethanol administration.ConclusionsThis beneficial effect of retigabine-ethanol interaction on memory may be a relevant element of the drug’s impact on the development of addiction.

Highlights

  • The new generation of antiepileptic drugs is a complex group characterized by multidirectional mechanisms of actions

  • Retigabine is an antiepileptic drug which mechanism of action is associated with the activation of voltage-gated potassium channels Kv7 [1]

  • The aim of this study was to assess the influence of retigabine on hippocampaldependent memory processes in rats receiving ethanol in various experimental models

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Summary

Introduction

The new generation of antiepileptic drugs is a complex group characterized by multidirectional mechanisms of actions For this reason, efforts are made to assess the possibility of their use in the therapy of neurological disorders other than epilepsy. We observed in our previous pharmaco-EEG study that retigabine decreased hippocampal ethanol-induced changes in the EEG rhythms in rabbits [13]. These results prompted us to continue research and this study is focused on assessing the interaction of ethanol and retigabine and their impact on memory processes related to the hippocampus. Results The drug significantly decreased ethanol-induced memory disturbances during alcohol administration as well as slightly improved learning processes after the discontinuation of ethanol administration. Conclusions This beneficial effect of retigabine-ethanol interaction on memory may be a relevant element of the drug’s impact on the development of addiction

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