{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T05:02:33Z","timestamp":1774069353319,"version":"3.50.1"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T00:00:00Z","timestamp":1593734400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T00:00:00Z","timestamp":1593734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The previous reports on an addiction vulnerability marker in the human SLC4A7 gene encoding the Na\/HCO<jats:sub>3<\/jats:sub> 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.<\/jats:p>","DOI":"10.1038\/s41598-020-67291-0","type":"journal-article","created":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T10:02:57Z","timestamp":1593770577000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Increased Alcohol Consumption in Mice Lacking Sodium Bicarbonate Transporter NBCn1"],"prefix":"10.1038","volume":"10","author":[{"given":"Jesse R.","family":"Schank","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soojung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos E.","family":"Gonzalez-Islas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadie E.","family":"Nennig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah D.","family":"Fulenwider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjun","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun Ming","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yejin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren A.","family":"Jeffers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaegwon","family":"Chung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Kyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Aalkjaer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebbe","family":"Boedtkjer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inyeong","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,7,3]]},"reference":[{"key":"67291_CR1","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1152\/physrev.00010.2003","volume":"83","author":"M Chesler","year":"2003","unstructured":"Chesler, M. Regulation and modulation of pH in the brain. Physiol. Rev. 83, 1183\u20131221 (2003).","journal-title":"Physiol. Rev."},{"key":"67291_CR2","unstructured":"Somjen, G. G. & Tombaugh, G. C. In pH and brain function (eds. K. Kaila & B. R. Ransom) 373\u2013393 (Wiley-Liss, 1998)."},{"key":"67291_CR3","unstructured":"Traynelis, S. F. In pH and Brain Function (eds. K. Kaila & B. R. Ransom) 417\u2013446, (Wiley-Liss, 1998)."},{"key":"67291_CR4","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1016\/j.febslet.2013.04.045","volume":"587","author":"A Sinning","year":"2013","unstructured":"Sinning, A. & Hubner, C. A. Minireview: pH and synaptic transmission. FEBS Lett. 587, 1923\u20131928, https:\/\/doi.org\/10.1016\/j.febslet.2013.04.045 (2013).","journal-title":"FEBS Lett."},{"key":"67291_CR5","doi-asserted-by":"crossref","unstructured":"Ruffin, V. A., Salameh, A. I., Boron, W. F. & Parker, M. D. Intracellular pH regulation by acid-base transporters in mammalian neurons. Front. Physiol.\u00a05, 43,\u00a0http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/24592239 (2014).","DOI":"10.3389\/fphys.2014.00043"},{"key":"67291_CR6","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.pneurobio.2016.02.002","volume":"138-140","author":"H Zhao","year":"2016","unstructured":"Zhao, H. et al. Emerging roles of Na+\/H+ exchangers in epilepsy and developmental brain disorders. Prog. Neurobiol. 138-140, 19\u201335, https:\/\/doi.org\/10.1016\/j.pneurobio.2016.02.002 (2016).","journal-title":"Prog. Neurobiol."},{"key":"67291_CR7","doi-asserted-by":"publisher","unstructured":"Pham, A. Q., Xu, L. H. & Moe, O. W. Drug-induced metabolic acidosis. F1000Res 4, https:\/\/doi.org\/10.12688\/f1000research.7006.1 (2015).","DOI":"10.12688\/f1000research.7006.1"},{"key":"67291_CR8","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1093\/bja\/85.1.136","volume":"85","author":"JA Henry","year":"2000","unstructured":"Henry, J. A. Metabolic consequences of drug misuse. Br. J. Anaesth. 85, 136\u2013142 (2000).","journal-title":"Br. J. Anaesth."},{"key":"67291_CR9","doi-asserted-by":"publisher","unstructured":"Palmer, B. F. & Clegg, D. J. Electrolyte disturbances in patients with chronic alcohol-use disorder. N. Engl. J. Med. 377, 1368\u20131377, https:\/\/doi.org\/10.1056\/NEJMra1704724 (2017).","DOI":"10.1056\/NEJMra1704724"},{"key":"67291_CR10","doi-asserted-by":"publisher","unstructured":"McGuire, L. C., Cruickshank, A. M. & Munro, P. T. Alcoholic ketoacidosis. Emerg. Med. J. 23, 417\u2013420, https:\/\/doi.org\/10.1136\/emj.2004.017590 (2006).","DOI":"10.1136\/emj.2004.017590"},{"key":"67291_CR11","first-page":"274","volume":"20","author":"M Elisaf","year":"1994","unstructured":"Elisaf, M., Merkouropoulos, M., Tsianos, E. V. & Siamopoulos, K. C. Acid-base and electrolyte abnormalities in alcoholic patients. Miner. Electrolyte Metab. 20, 274\u2013281 (1994).","journal-title":"Miner. Electrolyte Metab."},{"key":"67291_CR12","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/cphy.c13005","volume":"4","author":"C Aalkjaer","year":"2014","unstructured":"Aalkjaer, C., Boedtkjer, E., Choi, I. & Lee, S. Cation-coupled bicarbonate transporters. Compr. Physiol. 4, 1605\u20131637, https:\/\/doi.org\/10.1002\/cphy.c13005 (2014).","journal-title":"Compr. Physiol."},{"key":"67291_CR13","doi-asserted-by":"crossref","unstructured":"Park, H. J. et al. Neuronal expression of sodium\/bicarbonate cotransporter NBCn1 (SLC4A7) and its response to chronic metabolic acidosis. Am. J. Physiol. Cell Physiol. 298, C1018\u2013C1028 (2010).","DOI":"10.1152\/ajpcell.00492.2009"},{"key":"67291_CR14","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1086\/324467","volume":"69","author":"GR Uhl","year":"2001","unstructured":"Uhl, G. R., Liu, Q. R., Walther, D., Hess, J. & Naiman, D. Polysubstance abuse-vulnerability genes: genome scans for association, using 1,004 subjects and 1,494 single-nucleotide polymorphisms. Am. J. Hum. Genet. 69, 1290\u20131300 (2001).","journal-title":"Am. J. Hum. Genet."},{"key":"67291_CR15","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1111\/j.1360-0443.2007.01877.x","volume":"102","author":"H Ishiguro","year":"2007","unstructured":"Ishiguro, H., Walther, D., Arinami, T. & Uhl, G. R. Variation in a bicarbonate co-transporter gene family member SLC4A7 is associated with propensity to addictions: a study using fine-mapping and three samples. Addiction 102, 1320\u20131325 (2007).","journal-title":"Addiction"},{"key":"67291_CR16","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1152\/physiolgenomics.00112.2016","volume":"49","author":"HJ Park","year":"2017","unstructured":"Park, H. J., Lee, S., Ju, E., Jones, J. A. & Choi, I. Alternative transcription of sodium\/bicarbonate transporter SLC4A7 gene enhanced by single nucleotide polymorphisms. Physiol. Genomics 49, 167\u2013176, https:\/\/doi.org\/10.1152\/physiolgenomics.00112.2016 (2017).","journal-title":"Physiol. Genomics"},{"key":"67291_CR17","doi-asserted-by":"crossref","unstructured":"Cooper, D. S. et al. Sodium\/bicarbonate cotransporter NBCn1\/slc4a7 increases cytotoxicity in magnesium depletion in primary cultures of hippocampal neurons. Eur. J. Neurosci. 29, 437\u2013446 (2009).","DOI":"10.1111\/j.1460-9568.2008.06611.x"},{"key":"67291_CR18","doi-asserted-by":"publisher","unstructured":"Park, H. J., Gonzalez-Islas, C. E., Kang, Y., Li, J. M. & Choi, I. Deletion of the Na\/HCO3\u00a0transporter NBCn1 protects hippocampal neurons from NMDA-induced seizures and neurotoxicity in mice. Sci. Rep. 9, 15981, https:\/\/doi.org\/10.1038\/s41598-019-52413-0 (2019).","DOI":"10.1038\/s41598-019-52413-0"},{"key":"67291_CR19","first-page":"186","volume":"27","author":"AM White","year":"2003","unstructured":"White, A. M. What happened? Alcohol, memory blackouts, and the brain. Alcohol. Res. Health 27, 186\u2013196 (2003).","journal-title":"Alcohol. Res. Health"},{"key":"67291_CR20","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1161\/CIRCULATIONAHA.110.015974","volume":"124","author":"E Boedtkjer","year":"2011","unstructured":"Boedtkjer, E. et al. Disruption of Na+,HCO3\n\u2212 cotransporter NBCn1 (slc4a7) inhibits NO-mediated vasorelaxation, smooth muscle Ca2+ sensitivity, and hypertension development in mice. Circulation 124, 1819\u20131829 (2011).","journal-title":"Circulation"},{"key":"67291_CR21","doi-asserted-by":"publisher","unstructured":"Thomsen, A. B., Kim, S., Aalbaek, F., Aalkjaer, C. & Boedtkjer, E. Intracellular acidification alters myogenic responsiveness and vasomotion of mouse middle cerebral arteries. J. Cereb. Blood Flow. Metab. 34, 161\u2013168, https:\/\/doi.org\/10.1038\/jcbfm.2013.192 (2014).","DOI":"10.1038\/jcbfm.2013.192"},{"key":"67291_CR22","doi-asserted-by":"publisher","unstructured":"Singh, A. K. et al. Essential role of the electroneutral Na+-HCO3\n\u2212 cotransporter NBCn1 in murine duodenal acid-base balance and colonic mucus layer build-up in vivo. J. Physiol. 591, 2189\u20132204, https:\/\/doi.org\/10.1113\/jphysiol.2012.247874 (2013).","DOI":"10.1113\/jphysiol.2012.247874"},{"key":"67291_CR23","doi-asserted-by":"publisher","first-page":"2406","DOI":"10.1038\/nprot.2006.356","volume":"1","author":"S Kaech","year":"2006","unstructured":"Kaech, S. & Banker, G. Culturing hippocampal neurons. Nat. Protoc. 1, 2406\u20132415, https:\/\/doi.org\/10.1038\/nprot.2006.356 (2006).","journal-title":"Nat. Protoc."},{"key":"67291_CR24","doi-asserted-by":"publisher","first-page":"2210","DOI":"10.1021\/bi00578a012","volume":"18","author":"JA Thomas","year":"1979","unstructured":"Thomas, J. A., Buchsbaum, R. N., Zimniak, A. & Racker, E. Intracellular pH measurements in Ehrlich ascites tumor cells utilizing spectroscopic probes generated in situ. Biochemistry 18, 2210\u20132218 (1979).","journal-title":"Biochemistry"},{"key":"67291_CR25","doi-asserted-by":"publisher","unstructured":"Fulenwider, H. D., Nennig, S. E., Price, M. E., Hafeez, H. & Schank, J. R. Sex differences in aversion-resistant ethanol intake in mice. Alcohol. Alcohol. https:\/\/doi.org\/10.1093\/alcalc\/agz022 (2019).","DOI":"10.1093\/alcalc\/agz022"},{"key":"67291_CR26","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s00213-010-1775-1","volume":"209","author":"A Thorsell","year":"2010","unstructured":"Thorsell, A., Schank, J. R., Singley, E., Hunt, S. P. & Heilig, M. Neurokinin-1 receptors (NK1R:s), alcohol consumption, and alcohol reward in mice. Psychopharmacology 209, 103\u2013111, https:\/\/doi.org\/10.1007\/s00213-010-1775-1 (2010).","journal-title":"Psychopharmacology"},{"key":"67291_CR27","doi-asserted-by":"publisher","unstructured":"Nennig, S. E. et al. Selective lesioning of nuclear factor-\u03baB activated cells in the nucleus accumbens shell attenuates alcohol place preference. Neuropsychopharmacology 43, 1032\u20131040, https:\/\/doi.org\/10.1038\/npp.2017.214 (2018).","DOI":"10.1038\/npp.2017.214"},{"key":"67291_CR28","doi-asserted-by":"publisher","unstructured":"Smith, P., Jeffers, L. A. & Koval, M. Effects of different routes of endotoxin injury on barrier function in alcoholic lung syndrome. Alcohol. 80, 81\u201389,\u00a0https:\/\/doi.org\/10.1016\/j.alcohol.2018.08.007 (2018).","DOI":"10.1016\/j.alcohol.2018.08.007"},{"key":"67291_CR29","doi-asserted-by":"crossref","unstructured":"Damkier, H. H., Nielsen, S. & Praetorius, J. An anti-NH2-terminal antibody localizes NBCn1 to heart endothelia and skeletal and vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 290, H172\u2013H180 (2006).","DOI":"10.1152\/ajpheart.00713.2005"},{"key":"67291_CR30","unstructured":"Ruifrok, A. C. & Johnston, D. A. Quantification of histochemical staining by color deconvolution. Anal. Quant. Cytol. Histol. 23, 291\u2013299 (2001)."},{"key":"67291_CR31","doi-asserted-by":"publisher","unstructured":"Sheedy, D. et al. An Australian brain bank: a critical investment with a high return! Cell. Tissue Bank. 9, 205\u2013216, https:\/\/doi.org\/10.1007\/s10561-008-9076-1 (2008).","DOI":"10.1007\/s10561-008-9076-1"},{"key":"67291_CR32","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1007\/s10529-006-9127-2","volume":"28","author":"S Fleige","year":"2006","unstructured":"Fleige, S. et al. Comparison of relative mRNA quantification models and the impact of RNA integrity in quantitative real-time RT-PCR. Biotechnol. Lett. 28, 1601\u20131613, https:\/\/doi.org\/10.1007\/s10529-006-9127-2 (2006).","journal-title":"Biotechnol. Lett."},{"key":"67291_CR33","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.brainres.2006.11.026","volume":"1132","author":"S Johansson","year":"2007","unstructured":"Johansson, S. et al. Validation of endogenous controls for quantitative gene expression analysis: application on brain cortices of human chronic alcoholics. Brain Res. 1132, 20\u201328, https:\/\/doi.org\/10.1016\/j.brainres.2006.11.026 (2007).","journal-title":"Brain Res."},{"key":"67291_CR34","doi-asserted-by":"publisher","unstructured":"Jin, Z. et al. Selective changes of GABA(A) channel subunit mRNAs in the hippocampus and orbitofrontal cortex but not in prefrontal cortex of human alcoholics. Front. Cell. Neurosci. 5, 30, https:\/\/doi.org\/10.3389\/fncel.2011.00030 (2011).","DOI":"10.3389\/fncel.2011.00030"},{"key":"67291_CR35","doi-asserted-by":"publisher","first-page":"24","DOI":"10.3389\/fpsyt.2016.00024","volume":"7","author":"J Goodman","year":"2016","unstructured":"Goodman, J. & Packard, M. G. Memory Systems and the Addicted Brain. Front. Psychiatry 7, 24, https:\/\/doi.org\/10.3389\/fpsyt.2016.00024 (2016).","journal-title":"Front. Psychiatry"},{"key":"67291_CR36","doi-asserted-by":"crossref","unstructured":"Church, J. A change from HCO3\n\u2212CO2- to HEPES-buffered medium modifies membrane properties of rat CA1 pyramidal neurones in vitro. J. Physiol. 455, 51\u201371 (1992).","DOI":"10.1113\/jphysiol.1992.sp019290"},{"key":"67291_CR37","doi-asserted-by":"crossref","unstructured":"Tombaugh, G. C. & Somjen, G. G. Effects of extracellular pH on voltage-gated Na+, K+ and Ca2+ currents in isolated rat CA1 neurons. J. Physiol. 493, 719\u2013732 (1996).","DOI":"10.1113\/jphysiol.1996.sp021417"},{"key":"67291_CR38","doi-asserted-by":"publisher","unstructured":"Makani, S. & Chesler, M. Endogenous alkaline transients boost postsynaptic NMDA receptor responses in hippocampal CA1 pyramidal neurons. J. Neurosci. 27, 7438\u20137446, https:\/\/doi.org\/10.1523\/JNEUROSCI.2304-07.2007 (2007).","DOI":"10.1523\/JNEUROSCI.2304-07.2007"},{"key":"67291_CR39","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1007\/BF02244901","volume":"112","author":"JK Belknap","year":"1993","unstructured":"Belknap, J. K., Crabbe, J. C. & Young, E. R. Voluntary consumption of ethanol in 15 inbred mouse strains. Psychopharmacology 112, 503\u2013510 (1993).","journal-title":"Psychopharmacology"},{"key":"67291_CR40","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.1111\/j.1530-0277.2006.00248.x","volume":"30","author":"RI Melendez","year":"2006","unstructured":"Melendez, R. I., Middaugh, L. D. & Kalivas, P. W. Development of an alcohol deprivation and escalation effect in C57BL\/6J mice. Alcohol. Clin. Exp. Res. 30, 2017\u20132025, https:\/\/doi.org\/10.1111\/j.1530-0277.2006.00248.x (2006).","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"67291_CR41","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/7854_2011_162","volume":"13","author":"JC Crabbe","year":"2013","unstructured":"Crabbe, J. C., Kendler, K. S. & Hitzemann, R. J. Modeling the diagnostic criteria for alcohol dependence with genetic animal models. Curr. Top. Behav. Neurosci. 13, 187\u2013221, https:\/\/doi.org\/10.1007\/7854_2011_162 (2013).","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"67291_CR42","doi-asserted-by":"publisher","unstructured":"Loh, S. H. et al. The effect and underlying mechanism of ethanol on intracellular H(+) -equivalent membrane transporters in human aorta smooth muscle cells. Alcohol. Clin. Exp. Res. 39, 2302\u20132312, https:\/\/doi.org\/10.1111\/acer.12892 (2015).","DOI":"10.1111\/acer.12892"},{"key":"67291_CR43","doi-asserted-by":"publisher","unstructured":"Lee, S. P. et al. Expressional and functional characterization of intracellular pH regulators and effects of ethanol in human oral epidermoid carcinoma cells. Cell Physiol. Biochem. 47, 2056\u20132068, https:\/\/doi.org\/10.1159\/000491473 (2018).","DOI":"10.1159\/000491473"},{"key":"67291_CR44","doi-asserted-by":"publisher","unstructured":"Tsai, Y. T. et al. Functional characterization of transmembrane intracellular pH regulators and mechanism of alcohol-induced intracellular acidosis in human umbilical cord blood stem cell-like cells. J. Cardiovasc. Pharmacol. 58, 589\u2013601, https:\/\/doi.org\/10.1097\/FJC.0b013e3182300228 (2011).","DOI":"10.1097\/FJC.0b013e3182300228"},{"key":"67291_CR45","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1189\/jlb.72.6.1109","volume":"72","author":"K Song","year":"2002","unstructured":"Song, K. et al. Chronic ethanol consumption by mice results in activated splenic T cells. J. Leukoc. Biol. 72, 1109\u20131116 (2002).","journal-title":"J. Leukoc. Biol."},{"key":"67291_CR46","doi-asserted-by":"publisher","unstructured":"Spitzer, J. H. & Meadows, G. G. Modulation of perforin, granzyme A, and granzyme B in murine natural killer (NK), IL2 stimulated NK, and lymphokine-activated killer cells by alcohol consumption. Cell. Immunol.\u00a0194, 205\u2013212, https:\/\/doi.org\/10.1006\/cimm.1999.1511 (1999).","DOI":"10.1006\/cimm.1999.1511"},{"key":"67291_CR47","doi-asserted-by":"publisher","unstructured":"Downs, C. A., Trac, D., Brewer, E. M., Brown, L. A. & Helms, M. N. Chronic alcohol ingestion changes the landscape of the alveolar epithelium. Biomed. Res. Int. 2013, 470217, https:\/\/doi.org\/10.1155\/2013\/470217 (2013).","DOI":"10.1155\/2013\/470217"},{"key":"67291_CR48","doi-asserted-by":"publisher","first-page":"695","DOI":"10.3390\/nu4070695","volume":"4","author":"ML McCaskill","year":"2012","unstructured":"McCaskill, M. L. et al. Alcohol exposure alters mouse lung inflammation in response to inhaled dust. Nutrients 4, 695\u2013710, https:\/\/doi.org\/10.3390\/nu4070695 (2012).","journal-title":"Nutrients"},{"key":"67291_CR49","doi-asserted-by":"publisher","unstructured":"Yeligar, S. M., Harris, F. L., Hart, C. M. & Brown, L. A. Ethanol induces oxidative stress in alveolar macrophages via upregulation of NADPH oxidases. J. Immunol.\u00a0188, 3648\u20133657, https:\/\/doi.org\/10.4049\/jimmunol.1101278 (2012).","DOI":"10.4049\/jimmunol.1101278"},{"key":"67291_CR50","doi-asserted-by":"crossref","unstructured":"Jacobs, S. et al. Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability. Proc. Natl. Acad. Sci. USA 105, 311\u2013316 (2008).","DOI":"10.1073\/pnas.0705487105"},{"key":"67291_CR51","doi-asserted-by":"crossref","unstructured":"Sinning, A. et al. Synaptic glutamate release is modulated by the Na+-driven Cl\u2212\/HCO3\n\u2212 exchanger Slc4a8. J. Neurosci. 31, 7300\u20137311 (2011).","DOI":"10.1523\/JNEUROSCI.0269-11.2011"},{"key":"67291_CR52","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1113\/expphysiol.2009.048603","volume":"94","author":"HS Yang","year":"2009","unstructured":"Yang, H. S. et al. Inhibition of rat Na\/HCO3 cotransporter (NBCn1) function and expression by the alternative splic domain. Exp. Physiol. 94, 1114\u20131123 (2009).","journal-title":"Exp. Physiol."},{"key":"67291_CR53","doi-asserted-by":"publisher","unstructured":"Koob, G. F. Addiction is a reward deficit and stress surfeit disorder. Front. Psychiatry 4, 72, https:\/\/doi.org\/10.3389\/fpsyt.2013.00072 (2013).","DOI":"10.3389\/fpsyt.2013.00072"},{"key":"67291_CR54","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1152\/physrev.00013.2008","volume":"89","author":"R Spanagel","year":"2009","unstructured":"Spanagel, R. Alcoholism: a systems approach from molecular physiology to addictive behavior. Physiol. Rev. 89, 649\u2013705, https:\/\/doi.org\/10.1152\/physrev.00013.2008 (2009).","journal-title":"Physiol. Rev."},{"key":"67291_CR55","unstructured":"Prus, A. J., James, J. R. & Rosecrans, J. A. In Methods of Behavior Analysis in Neuroscience (eds. J. J. Buccafusco) Ch. 4 (CRC Press, 2009)."},{"key":"67291_CR56","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/nrn1406","volume":"5","author":"RA Wise","year":"2004","unstructured":"Wise, R. A. Dopamine, learning and motivation. Nat. Rev. Neurosci. 5, 483\u2013494, https:\/\/doi.org\/10.1038\/nrn1406 (2004).","journal-title":"Nat. Rev. Neurosci."},{"key":"67291_CR57","unstructured":"Ron, D. & Wang, J. In Biology of the NMDA Receptor (ed. A. M. Van Dongen) 60\u201376 (CRC Press, 2009)."},{"key":"67291_CR58","first-page":"298","volume":"31","author":"AZ Pietrzykowski","year":"2008","unstructured":"Pietrzykowski, A. Z. & Treistman, S. N. The molecular basis of tolerance. Alcohol. Res. Health 31, 298\u2013309 (2008).","journal-title":"Alcohol. Res. Health"},{"key":"67291_CR59","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1016\/j.neuropharm.2010.12.028","volume":"61","author":"BA McCool","year":"2011","unstructured":"McCool, B. A. Ethanol modulation of synaptic plasticity. Neuropharmacology 61, 1097\u20131108, https:\/\/doi.org\/10.1016\/j.neuropharm.2010.12.028 (2011).","journal-title":"Neuropharmacology"},{"key":"67291_CR60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.alcohol.2013.09.045","volume":"48","author":"CF Zorumski","year":"2014","unstructured":"Zorumski, C. F., Mennerick, S. & Izumi, Y. Acute and chronic effects of ethanol on learning-related synaptic plasticity. Alcohol 48, 1\u201317, https:\/\/doi.org\/10.1016\/j.alcohol.2013.09.045 (2014).","journal-title":"Alcohol"},{"key":"67291_CR61","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1038\/nn1105-1442","volume":"8","author":"GF Koob","year":"2005","unstructured":"Koob, G. F. & Le Moal, M. Plasticity of reward neurocircuitry and the \u2018dark side\u2019 of drug addiction. Nat. Neurosci. 8, 1442\u20131444, https:\/\/doi.org\/10.1038\/nn1105-1442 (2005).","journal-title":"Nat. Neurosci."},{"key":"67291_CR62","doi-asserted-by":"publisher","unstructured":"Smith, D. M. & Atkinson, R. M. Alcoholism and dementia. Int. J. Addict. 30, 1843\u20131869, https:\/\/doi.org\/10.3109\/10826089509071058 (1995).","DOI":"10.3109\/10826089509071058"},{"key":"67291_CR63","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1016\/j.nlm.2011.01.003","volume":"96","author":"RP Vetreno","year":"2011","unstructured":"Vetreno, R. P., Hall, J. M. & Savage, L. M. Alcohol-related amnesia and dementia: animal models have revealed the contributions of different etiological factors on neuropathology, neurochemical dysfunction and cognitive impairment. Neurobiol. Learn. Mem. 96, 596\u2013608, https:\/\/doi.org\/10.1016\/j.nlm.2011.01.003 (2011).","journal-title":"Neurobiol. Learn. Mem."},{"key":"67291_CR64","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/s0301-0082(98)00060-4","volume":"56","author":"TM Tzschentke","year":"1998","unstructured":"Tzschentke, T. M. Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues. Prog. Neurobiol. 56, 613\u2013672, https:\/\/doi.org\/10.1016\/s0301-0082(98)00060-4 (1998).","journal-title":"Prog. Neurobiol."},{"key":"67291_CR65","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s00213-003-1559-y","volume":"170","author":"CL Cunningham","year":"2003","unstructured":"Cunningham, C. L., Ferree, N. K. & Howard, M. A. Apparatus bias and place conditioning with ethanol in mice. Psychopharmacology 170, 409\u2013422, https:\/\/doi.org\/10.1007\/s00213-003-1559-y (2003).","journal-title":"Psychopharmacology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67291-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67291-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67291-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T13:17:18Z","timestamp":1670332638000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67291-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,3]]},"references-count":65,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["67291"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-67291-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,3]]},"assertion":[{"value":"23 November 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11017"}}