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Abstract
Background: Activation of Kv7 potassium channels may decrease the reactivity of mesolimbic dopaminergic neurons that are implicated in mediating the reinforcing effects of ethanol. Objectives: The objective of this study was to determine whether the administration of the Kv7 potassium channel opener retigabine would decrease ethanol intake in Long Evans rats. Methods: A limited access two-bottle choice model of alcohol (10% solution) consumption was used in this study. A separate group of animals was tested to evaluate the actions of retigabine on sucrose (5% solution) consumption to determine whether this drug might produce non-selective impairment of the ability of rats to drink liquids. Animals were treated with either vehicle or increasing doses (2.5–7.5 mg/kg SC) of retigabine administered over a 3-day period. Results: Compared to vehicle, retigabine at a dose of 7.5 mg/kg produced a reduction in the amount of ethanol consumed. These effects did not occur in association with significant changes in water consumption. A significant time effect was found for the actions of retigabine in sucrose-drinking rats with a trend for an increase in sucrose intake with the highest dose of retigabine administered. Conclusions: These results indicate that the administration of retigabine may produce a decrease in ethanol consumption by rats at doses that do not significantly reduce the drinking of either water or a sucrose solution. These findings are consistent with the hypothesis that activation of Kv7 channels facilitates the reduction of alcohol consumption in the rat.
Acknowledgements
This work was supported by the NIH Grant R01AA015923 to DAC and by funds received from the Gennaro Acampora Charitable Trust Fund to CMK.