Knapp Clifford M, O'Malley Matthew, Datta Subimal, Ciraulo Domenic A
BUPA Clinical Studies Unit .
Am J Drug Alcohol Abuse. 2014 May;40(3):244-50. doi: 10.3109/00952990.2014.892951. Epub 2014 Apr 15.
Activation of Kv7 potassium channels may decrease the reactivity of mesolimbic dopaminergic neurons that are implicated in mediating the reinforcing effects of ethanol.
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.
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.
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.
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.
Kv7钾通道的激活可能会降低中脑边缘多巴胺能神经元的反应性,这些神经元与介导乙醇的强化作用有关。
本研究的目的是确定给予Kv7钾通道开放剂瑞替加滨是否会减少Long Evans大鼠的乙醇摄入量。
本研究采用酒精(10%溶液)消耗的有限接触双瓶选择模型。对另一组动物进行测试,以评估瑞替加滨对蔗糖(5%溶液)消耗的作用,以确定该药物是否可能对大鼠饮用液体的能力产生非选择性损害。动物在3天内接受载体或递增剂量(2.5 - 7.5mg/kg皮下注射)的瑞替加滨治疗。
与载体相比,7.5mg/kg剂量的瑞替加滨使乙醇消耗量减少。这些作用并未伴随着饮水量的显著变化而出现。在饮用蔗糖的大鼠中,发现瑞替加滨的作用存在显著的时间效应,随着给予最高剂量的瑞替加滨,蔗糖摄入量有增加的趋势。
这些结果表明,给予瑞替加滨可能会使大鼠的乙醇消耗量减少,且该剂量不会显著降低水或蔗糖溶液的饮用量。这些发现与Kv7通道激活促进大鼠酒精消耗量减少的假设一致。