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The kinase IKK\u03b2 mediates the phosphorylation and subsequent proteasomal degradation of cytosolic protein inhibitors of NF-\u03baB, leading to activation of NF-\u03baB. The role of IKK\u03b2 as a potential regulator of excessive alcohol drinking had not previously been investigated. Based on previous findings that the overactivation of innate immune\/inflammatory signaling promotes ethanol consumption, we hypothesized that inhibiting IKK\u03b2 would limit\/decrease drinking by preventing the activation of NF-\u03baB. We studied the systemic effects of two pharmacological inhibitors of IKK\u03b2, TPCA-1 and sulfasalazine, on ethanol intake using continuous- and limited-access, two-bottle choice drinking tests in C57BL\/6J mice. In both tests, TPCA-1 and sulfasalazine reduced ethanol intake and preference without changing total fluid intake or sweet taste preference. A virus expressing<jats:italic>Cre<\/jats:italic>recombinase was injected into the nucleus accumbens and central amygdala to selectively knock down IKK\u03b2 in mice genetically engineered with a conditional<jats:italic>Ikkb<\/jats:italic>deletion (<jats:italic>Ikkb<jats:sup>F\/F<\/jats:sup><\/jats:italic>). Although IKK\u03b2 was inhibited to some extent in astrocytes and microglia, neurons were a primary cellular target. Deletion of IKK\u03b2 in either brain region reduced ethanol intake and preference in the continuous access two-bottle choice test without altering the preference for sucrose. Pharmacological and genetic inhibition of IKK\u03b2 decreased voluntary ethanol consumption, providing initial support for IKK\u03b2 as a potential therapeutic target for alcohol abuse.<\/jats:p>","DOI":"10.1523\/eneuro.0256-16.2016","type":"journal-article","created":{"date-parts":[[2016,10,20]],"date-time":"2016-10-20T01:13:32Z","timestamp":1476926012000},"page":"ENEURO.0256-16.2016","source":"Crossref","is-referenced-by-count":37,"title":["Inhibition of IKK\u03b2 Reduces Ethanol Consumption in C57BL\/6J Mice"],"prefix":"10.1523","volume":"3","author":[{"given":"Jay M.","family":"Truitt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri A.","family":"Blednov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jillian M.","family":"Benavidez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mendy","family":"Black","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Ponomareva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jade","family":"Law","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6459-3541","authenticated-orcid":false,"given":"Morgan","family":"Merriman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2601-6372","authenticated-orcid":false,"given":"Sami","family":"Horani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Jameson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy W.","family":"Lasek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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