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Although acamprosate is known to stabilize the hyper\u2010glutamatergic state in alcoholism, pharmacological mechanisms of action in brain tissue remains unknown. To investigate the mechanism of acamprosate efficacy, the authors employ a pharmacoproteomics approach using an animal model of alcoholism, type 1 equilibrative nucleoside transporter (ENT1) null mice. The results demonstrate that acamprosate treatment significantly decreased both ethanol drinking and preference in ENT1 null mice compared to that of wild\u2010type mice. Then, to elucidate acamprosate efficacy mechanism in ENT1 null mice, the authors utilize label\u2010free quantification proteomics comparing both genotype and acamprosate treatment effects in the nucleus accumbens (NAc). A total of 1040 protein expression changes are identified in the NAc among 3634 total proteins detected. The proteomics and Western blot result demonstrate that acamprosate treatment decreased EAAT expression implicating stabilization of the hyper\u2010glutamatergic condition in ENT1 null mice. Pathway analysis suggests that acamprosate treatment in ENT1 null mice seems to rescue glutamate toxicity through restoring of RTN4 and NF\u2010\u03baB medicated neuroimmune signaling compared to wild\u2010type mice. Overall, pharmacoproteomics approaches suggest that neuroimmune restoration is a potential efficacy mechanism in the acamprosate treatment of certain sub\u2010populations of alcohol dependent subjects.<\/jats:p>","DOI":"10.1002\/pmic.201700417","type":"journal-article","created":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T10:33:10Z","timestamp":1518517990000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pharmacoproteomics Profile in Response to Acamprosate Treatment of an Alcoholism Animal Model"],"prefix":"10.1002","volume":"18","author":[{"given":"Caroline E.","family":"Germany","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Neuroscience Louisiana State University Health Sciences Center  Shreveport LA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashlie N.","family":"Reker","sequence":"additional","affiliation":[{"name":"Department of 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