<?xml version='1.0' encoding='UTF-8'?><xml><records><record><source-app name="HighWire" version="7.x">Drupal-HighWire</source-app><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Truitt, Jay M.</style></author><author><style face="normal" font="default" size="100%">Blednov, Yuri A.</style></author><author><style face="normal" font="default" size="100%">Benavidez, Jillian M.</style></author><author><style face="normal" font="default" size="100%">Black, Mendy</style></author><author><style face="normal" font="default" size="100%">Ponomareva, Olga</style></author><author><style face="normal" font="default" size="100%">Law, Jade</style></author><author><style face="normal" font="default" size="100%">Merriman, Morgan</style></author><author><style face="normal" font="default" size="100%">Horani, Sami</style></author><author><style face="normal" font="default" size="100%">Jameson, Kelly</style></author><author><style face="normal" font="default" size="100%">Lasek, Amy W.</style></author><author><style face="normal" font="default" size="100%">Harris, R. Adron</style></author><author><style face="normal" font="default" size="100%">Mayfield, R. Dayne</style></author></authors><secondary-authors></secondary-authors></contributors><titles><title><style face="normal" font="default" size="100%">Inhibition of IKKβ Reduces Ethanol Consumption in C57BL/6J Mice</style></title><secondary-title><style face="normal" font="default" size="100%">eneuro</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2016</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2016-09-01 00:00:00</style></date></pub-dates></dates><elocation-id><style  face="normal" font="default" size="100%">ENEURO.0256-16.2016</style></elocation-id><doi><style  face="normal" font="default" size="100%">10.1523/ENEURO.0256-16.2016</style></doi><volume><style face="normal" font="default" size="100%">3</style></volume><issue><style face="normal" font="default" size="100%">5</style></issue><abstract><style  face="normal" font="default" size="100%">Proinflammatory pathways in neuronal and non-neuronal cells are implicated in the acute and chronic effects of alcohol exposure in animal models and humans. The nuclear factor-κB (NF-κB) family of DNA transcription factors plays important roles in inflammatory diseases. The kinase IKKβ mediates the phosphorylation and subsequent proteasomal degradation of cytosolic protein inhibitors of NF-κB, leading to activation of NF-κB. The role of IKKβ 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 IKKβ would limit/decrease drinking by preventing the activation of NF-κB. We studied the systemic effects of two pharmacological inhibitors of IKKβ, 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 Cre recombinase was injected into the nucleus accumbens and central amygdala to selectively knock down IKKβ in mice genetically engineered with a conditional Ikkb deletion (IkkbF/F). Although IKKβ was inhibited to some extent in astrocytes and microglia, neurons were a primary cellular target. Deletion of IKKβ 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 IKKβ decreased voluntary ethanol consumption, providing initial support for IKKβ as a potential therapeutic target for alcohol abuse.</style></abstract></record></records></xml>