Increased Alcohol Consumption in Mice Lacking Sodium Bicarbonate Transporter NBCn1

• Type of Material: Article
• Authors: Jesse R. Schank, University of Georgia; Soojung Lee, Emory University; Carlos Gonzalez Islas, Emory University; Sadie E. Nennig, University of Georgia; Hannah D. Fulenwider, University of Georgia; Jianjun Chang, Emory University; Jun Ming Li, Emory University; Yeijn Kim, Emory University; Lauren A. Jeffers, Emory University; Jaegwon Chung, University of Georgia; Jae-Kyung Lee, University of Georgia; Zhe Jin, Uppsala University; Christian Aalkjaer, Aarhus University; Ebbe Boedtkjer, Aarhus University; Inyeong Choi, Emory University
• Language: English
• Date: 2020-07-03
• Publisher: Springer Nature Ltd.
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-020-67291-0
• Title of Journal or Parent Work: Scientific Reports
• Volume: 10
• Issue: 1
• Start Page: 11017
• End Page: 11017
• Grant/Funding Information: Te work was supported by the National Institute of Health Pathway to Independence Award [AA021805] and the University of Georgia (J.R.S.) and by the NIH [GM078502-S], Emory University Research Committee and American Heart Association [14GRNT20480379] (I.C.).
• Keywords: Expression; Intracellular pH Regulators; Ethanol; Quantification; Multidisciplinary Sciences; Mechanism; Functional characterization; Disruption; Cotransporter NBCN1; Science & Technology; SLC4A7; Science & Technology - Other Topics; Modulation
• Research Categories: Psychology, Behavioral; Health Sciences, Nutrition; Health Sciences, Toxicology; Biology, Neuroscience

Abstract

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.