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Here we demonstrate that rats subjected to repeated cycles of intoxication and withdrawal develop a marked and long\u2010lasting increase in voluntary ethanol intake. Exposure\u2010induced but not spontaneous alcohol intake is antagonized by acamprosate, a compound clinically effective in human alcoholism. Expression analysis of cingulate cortex and amygdala reveals a set of long\u2010term up\u2010regulated transcripts in this model. These include members of pathways previously implicated in alcohol dependence (glutamatergic, endocan\u2010nabinoid, and monoaminergic neurotransmission), as well as pathways not previously thought to be involved in this disorder (e.g., members of the mitogen\u2010activated protein kinase pathway). Thus, alternating periods of ethanol intoxication and withdrawal are sufficient to induce an altered functional brain state, which is likely to be encoded by long\u2010term changes in gene expression. These observations may have important implications for how alcoholism is managed clinically. Novel clinically effective treatments may be possible to develop by targeting the products of genes found to be regulated in our model.\u2014Rimondini, R., Arlinde, C., Sommer, W., Heilig, M. Long\u2010lasting increase in voluntary ethanol consumption and transcriptional regulation in the rat brain after intermittent exposure to alcohol.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    16, 27\u201335 (2002)\n                  <\/jats:p>","DOI":"10.1096\/fj.01-0593com","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T19:03:24Z","timestamp":1027710204000},"page":"27-35","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":275,"title":["Long\u2010lasting increase in voluntary ethanol consumption and transcriptional regulation in the rat brain after intermittent exposure to alcohol"],"prefix":"10.1096","volume":"16","author":[{"given":"Roberto","family":"Rimondini","sequence":"first","affiliation":[{"name":"NEUROTEC Karolinska Institutet Stockholm 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