Increased Alcohol Consumption in Mice Lacking Sodium Bicarbonate Transporter NBCn1
Autor: | Jun Ming Li, Lauren A. Jeffers, Soojung Lee, Yejin Kim, Carlos Gonzalez-Islas, Sadie E. Nennig, Jaegwon Chung, Jae-Kyung Lee, Zhe Jin, Jianjun Chang, Ebbe Boedtkjer, Inyeong Choi, Hannah D. Fulenwider, Christian Aalkjaer, Jesse R. Schank |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Male
medicine.medical_specialty Sucrose Alcohol Drinking Intracellular pH Hippocampus Addiction Down-Regulation lcsh:Medicine Alcohol Striatum Hippocampal formation Transport carrier Article chemistry.chemical_compound Gene Knockout Techniques Mice Internal medicine medicine Animals Humans lcsh:Science Cells Cultured Neurons Multidisciplinary Quinine Chemistry Sodium-Bicarbonate Symporters lcsh:R Neurosciences Hydrogen-Ion Concentration Conditioned place preference Endocrinology Knockout mouse lcsh:Q Neurovetenskaper Addiction vulnerability |
Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020) Schank, J R, Lee, S, Gonzalez-Islas, C E, Nennig, S E, Fulenwider, H D, Chang, J, Li, J M, Kim, Y, Jeffers, L A, Chung, J, Lee, J-K, Jin, Z, Aalkjær, C, Boedtkjer, E & Choi, I 2020, ' Increased Alcohol Consumption in Mice Lacking Sodium Bicarbonate Transporter NBCn1 ', Scientific Reports, vol. 10, no. 1, 11017 . https://doi.org/10.1038/s41598-020-67291-0 Scientific Reports |
Popis: | 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. |
Databáze: | OpenAIRE |
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