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This project assessed whether chronic exposure to alcohol can increase cerebral oxidation of acetate. Through metabolism, acetate may contribute to long\u2010term adaptation to drinking. Two groups of adult male Sprague\u2013Dawley rats were studied, one treated with ethanol vapor and the other given room air. After 3\u00a0weeks the rats received an intravenous infusion of [2\u2010<jats:sup>13<\/jats:sup>C]ethanol via a lateral tail vein for 2\u00a0h. As the liver converts ethanol to [2\u2010<jats:sup>13<\/jats:sup>C]acetate, some of the acetate enters the brain. Through oxidation the <jats:sup>13<\/jats:sup>C is incorporated into the metabolic intermediate \u03b1\u2010ketoglutarate, which is converted to glutamate (Glu), glutamine (Gln), and <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>. These were observed by magnetic resonance spectroscopy and found to be <jats:sup>13<\/jats:sup>C\u2010labeled primarily through the consumption of ethanol\u2010derived acetate. Brain Gln, Glu, and, <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content> <jats:sup>13<\/jats:sup>C enrichments, normalized to <jats:sup>13<\/jats:sup>C\u2010acetate enrichments in the plasma, were higher in the chronically treated rats than in the ethanol\u2010na\u00efve rats, suggesting increased cerebral uptake and oxidation of circulating acetate. Chronic ethanol exposure increased incorporation of systemically derived acetate into brain Gln, Glu, and <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>, key neurochemicals linked to brain energy metabolism and neurotransmission.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12405-fig-0006-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><jats:p>The liver converts ethanol to acetate, which may contribute to long\u2010term adaptation to drinking. Astroglia oxidize acetate and generate neurochemicals, while neurons and glia may also oxidize ethanol. When <jats:sup>13<\/jats:sup>C\u2010ethanol is administered intravenously, <jats:sup>13<\/jats:sup>C\u2010glutamine, glutamate, and GABA, normalized to <jats:sup>13<\/jats:sup>C\u2010acetate, were higher in chronic ethanol\u2010exposed rats than in control rats, suggesting that ethanol exposure increases cerebral oxidation of circulating acetate.\n<\/jats:p>","DOI":"10.1111\/jnc.12405","type":"journal-article","created":{"date-parts":[[2013,8,19]],"date-time":"2013-08-19T08:20:40Z","timestamp":1376900440000},"page":"353-364","source":"Crossref","is-referenced-by-count":15,"title":["Metabolic products of [2\u2010<sup>13<\/sup>C]ethanol in the rat brain after chronic ethanol exposure"],"prefix":"10.1111","volume":"127","author":[{"given":"Jie","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Wuhan Institute of Physics and Mathematics Chinese Academy of Science Wuhan Hubei China"},{"name":"Department of Diagnostic Radiology School of Medicine Yale University New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology School of Medicine Yale University New Haven Connecticut USA"},{"name":"College of Food Science and Technology and the MOE Key Laboratory of Environment Correlative Dietology Huazhong Agricultural University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxian","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology School of Medicine Yale University New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Pittman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry School of Medicine Yale University New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Castracane","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology School of Medicine Yale University New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting\u2010Kai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Duke University School of Medicine Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin L.","family":"Behar","sequence":"additional","affiliation":[{"name":"Department of Psychiatry School of Medicine Yale University New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme F.","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology School of Medicine Yale University New Haven Connecticut USA"},{"name":"Department of Psychiatry School of Medicine Yale University New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,9,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(92)90042-H"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2010.01379.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02435024"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-8329(96)00067-5"},{"key":"e_1_2_9_6_1","volume-title":"Nonparametric analysis of longitudinal data in factorial experiments","author":"Brunner E.","year":"2002"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1983.244.3.C270"},{"key":"e_1_2_9_8_1","first-page":"403","article-title":"Central nervous system effects of acetate: Contribution to the central effects of ethanol","volume":"259","author":"Carmichael F. 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