Ewa Zwierzyńska1, Agata Krupa-Burtnik2, Bogusława Pietrzak2. 1. Department of Pharmacodynamics, Medical University of Lodz, Muszyńskiego 1, 90-151, Łódź, Poland. ewa.zwierzynska@umed.lodz.pl. 2. Department of Pharmacodynamics, Medical University of Lodz, Muszyńskiego 1, 90-151, Łódź, Poland.
Abstract
BACKGROUND: 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. METHODS: 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. 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.
BACKGROUND: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 ethanolabuse 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. METHODS: 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. 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.
Authors: Svenja E Sander; Mustansir Diwan; Roger Raymond; José N Nobrega; Angelika Richter Journal: CNS Neurol Disord Drug Targets Date: 2016 Impact factor: 4.388