Silva-Cardoso Gleice Kelli, N'Gouemo Prosper
Howard University College of Medicine, Department of Physiology and Biophysics, Washington, DC, 20059, United States of America.
Howard University College of Medicine, Department of Physiology and Biophysics, Washington, DC, 20059, United States of America.
Neuropharmacology. 2025 Sep 1;275:110498. doi: 10.1016/j.neuropharm.2025.110498. Epub 2025 May 3.
Repeated episodes of binge drinking can lead to an alcohol use disorder, yet the underlying pharmacological mechanisms are still not fully understood. Nevertheless, emerging evidence indicates that Ca-dependent signaling effectively reduces alcohol consumption without affecting water intake. Therefore, activating anoctamin1 (ANO1), a Ca-activated chloride channel and a component of Ca-dependent signaling, can similarly decrease alcohol drinking while maintaining normal water intake. This study investigates how activation of ANO1 channels with EACT affects voluntary alcohol consumption in male and female Sprague-Dawley rats using the intermittent alcohol access method in a two-bottle choice paradigm. Rats were trained to drink 7.5 % ethanol or water for four weeks before administering either EACT (2.5, 5, and 10 mg/kg). Afterward, their alcohol intake, preference, and water intake were systematically recorded 2 and 24 h after exposure to water and 7.5 % ethanol solution. The results indicated that female rats consumed more alcohol than males. Furthermore, activating ANO1 channels with EACT significantly decreased alcohol intake and preference in males, only at the 5 mg/kg dose; in females, this effect was observed as a linear response at both the 5 and 10 mg/kg doses, highlighting distinct sex-related differences. Additionally, the inhibitory effect of EACT on alcohol consumption was associated with increased water intake in females, suggesting a potential influence of EACT on thirst homeostasis. Collectively, these findings highlight the differential effects of EACT on alcohol intake, preference, and water intake based on sex, and underscore the complexity of consummatory behavior mechanisms.
反复暴饮可导致酒精使用障碍，但其潜在的药理学机制仍未完全明确。然而，新出现的证据表明，钙依赖信号传导可有效减少酒精摄入量，而不影响水的摄入量。因此，激活八聚体通道蛋白1（ANO1），一种钙激活氯离子通道和钙依赖信号传导的组成部分，同样可以在维持正常水摄入的同时减少酒精饮用。本研究使用双瓶选择范式中的间歇性酒精摄入方法，探究用伊佛卡因（EACT）激活ANO1通道如何影响雄性和雌性斯普拉格-道利大鼠的自愿酒精摄入量。在给予EACT（2.5、5和10mg/kg）之前，大鼠接受四周饮用7.5%乙醇或水的训练。之后，在大鼠接触水和7.5%乙醇溶液2小时和24小时后，系统记录它们的酒精摄入量、偏好和水摄入量。结果表明，雌性大鼠比雄性大鼠摄入更多酒精。此外，仅在5mg/kg剂量下，用EACT激活ANO1通道可显著降低雄性大鼠的酒精摄入量和偏好；在雌性大鼠中，在5mg/kg和10mg/kg剂量下均观察到这种效应呈线性反应，突出了明显的性别差异。此外，EACT对酒精摄入的抑制作用与雌性大鼠水摄入量增加有关，表明EACT对渴觉稳态有潜在影响。总的来说，这些发现突出了EACT对基于性别的酒精摄入量、偏好和水摄入量的不同影响，并强调了消费行为机制的复杂性。
