The previous reports on an addiction vulnerability marker in the human SLC4A7 gene encoding the Na/HCO₃ transporter NBCn1 suggest that this pH-regulating protein may affect alcohol-related behavior and response. Here, we examined alcohol consumption and sensitivity to the sedative effects of alcohol in male NBCn1 knockout mice. These mice displayed lower pH in neurons than wildtype controls, determined by intracellular pH in hippocampal neuronal cultures. Neurons from knockout mice had a higher action potential threshold and a more depolarized membrane potential, thus reducing membrane excitability. In a two-bottle free choice procedure, knockout mice consumed more alcohol than controls and consistently increased alcohol consumption after repeated alcohol deprivation periods. Quinine and sucrose preference was similar between genotypes. Knockout mice showed increased propensity for alcohol-induced conditioned place preference. In loss of righting reflex assessment, knockout mice revealed increased sensitivity to alcohol-induced sedation and developed tolerance to the sedation after repeated alcohol administrations. Furthermore, chronic alcohol consumption caused NBCn1 downregulation in the hippocampus and striatum of mice and humans. These results demonstrate an important role of NBCn1 in regulation of alcohol consumption and sensitivity to alcohol-induced sedation.

以前的报道涉及人类Na / HCO ₃编码SLC4A7基因中的成瘾易感性标记转运蛋白NBCn1提示此pH调节蛋白可能会影响酒精相关的行为和反应。在这里，我们检查了雄性NBCn1基因敲除小鼠的饮酒量和对酒精镇静作用的敏感性。根据海马神经元培养物中的细胞内pH值确定，这些小鼠的神经元pH值低于野生型对照。基因敲除小鼠的神经元具有较高的动作电位阈值和更去极化的膜电位，从而降低了膜的兴奋性。在两瓶免费选择程序中，基因敲除的小鼠比对照组消耗更多的酒精，并且在反复饮酒后不断增加酒精的消耗。奎宁和蔗糖的偏好在基因型之间是相似的。敲除小鼠显示出酒精诱导的条件性场所偏好的倾向增加。在丧失对正反射能力的评估中，基因敲除小鼠显示出对酒精诱导的镇静的敏感性增加，并且在重复饮酒后对镇静产生了耐受性。此外，长期饮酒会导致小鼠和人类海马和纹状体中NBCn1的下调。这些结果证明了NBCn1在调节饮酒量和对酒精引起的镇静敏感性方面的重要作用。