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We exploited the rapid development of physical dependence in\n                      <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                      (\n                      <jats:italic>C. elegans<\/jats:italic>\n                      ) to examine the ethanol\u2010induced transcriptional changes that correspond with physical dependence and withdrawal effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>After an 18\u2010h exposure to an intoxicating concentration of ethanol, we observe the development of physical dependence; withdrawal from ethanol causes an increase in their preference for thicker parts of a bacterial lawn, a behavior we term withdrawal\u2010induced bordering (WIB). We performed transcriptional analysis to identify genes whose expression changes correlate with WIB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that WIB is transient, resolving within 6\u2009h of removal from ethanol, suggesting it is driven by short\u2010term gene expression changes. We identified 1870 genes with differential expression immediately after ethanol exposure but not after 6\u2009h of withdrawal; these are candidate mediators of WIB. We found that the SWI\/SNF chromatin remodeling complex, known to be important in the response to acute ethanol exposure, is required for normal WIB. Loss of\n                      <jats:italic>swsn\u20109<\/jats:italic>\n                      attenuated but did not eliminate WIB, suggesting that there are\n                      <jats:italic>swsn\u20109<\/jats:italic>\n                      \u2010dependent and\n                      <jats:italic>swsn\u20109<\/jats:italic>\n                      \u2010independent components of WIB. Regulation of 1031 ethanol\u2010responsive genes requires\n                      <jats:italic>swsn\u20109<\/jats:italic>\n                      . WIB phenocopies reduced\n                      <jats:italic>npr\u20101<\/jats:italic>\n                      activity, and two genes implicated in the\n                      <jats:italic>npr\u20101<\/jats:italic>\n                      signaling pathway,\n                      <jats:italic>jmjc\u20101<\/jats:italic>\n                      and\n                      <jats:italic>dod\u201024<\/jats:italic>\n                      , were transiently regulated after extended ethanol exposure.\n                      <jats:italic>dod\u201024<\/jats:italic>\n                      mutants have attenuated WIB.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Extended exposure to ethanol causes the development of transient physical dependence in\n                      <jats:italic>C. elegans<\/jats:italic>\n                      , and the SWI\/SNF complex is involved in this process. Genes involved in fatty acid metabolism were regulated over the WIB timecourse, and\n                      <jats:italic>dod\u201024<\/jats:italic>\n                      , which is involved in temperature sensitivity, is required for normal WIB. Together, these results suggest a model in which modulation of lipid membrane composition may be one mechanism for the development of physical dependence on ethanol.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70223","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T08:24:35Z","timestamp":1768292675000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>SWI<\/scp>\n                    \/\n                    <scp>SNF<\/scp>\n                    complexes modulate gene expression and the development of physical dependence to ethanol"],"prefix":"10.1111","volume":"50","author":[{"given":"Laura D.","family":"Mathies","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University  Richmond Virginia USA"},{"name":"Virginia Commonwealth University Alcohol Research Center  Richmond 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