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However, the specific molecular mechanisms driving its inhibitory effects on cue\u2010induced nicotine reinstatement are unknown. Here, we confirm that extinction of nicotine\u2010seeking behavior is associated with impaired NAcore GLT\u20101 function and expression and demonstrates that reinstatement of nicotine seeking rapidly enhances membrane fraction GLT\u20101 expression. Extinction and cue\u2010induced reinstatement of nicotine seeking was also associated with increased tumor necrosis factor alpha (TNF\u03b1) and decreased glial fibrillary acidic protein (GFAP) expression in the NAcore. NAC treatment (100 mg\/kg\/day, i.p., for 5 d) inhibited cue\u2010induced nicotine seeking and suppressed AMPA to NMDA current ratios, suggesting that NAC reduces NAcore postsynaptic excitability. In separate experiments, rats received NAC and an antisense vivo\u2010morpholino to selectively suppress GLT\u20101 expression in the NAcore during extinction and were subsequently tested for cue\u2010induced reinstatement of nicotine seeking. NAC treatment rescued NAcore GLT\u20101 expression and attenuated cue\u2010induced nicotine seeking, which was blocked by GLT\u20101 antisense. NAC also reduced TNF\u03b1 expression in the NAcore. Viral manipulation of the NF\u2010\u03baB pathway, which is downstream of TNF\u03b1, revealed that cue\u2010induced nicotine seeking is regulated by NF\u2010\u03baB pathway signaling in the NAcore independent of GLT\u20101 expression. Ultimately, these results are the first to show that immunomodulatory mechanisms may regulate known nicotine\u2010induced alterations in glutamatergic plasticity that mediate cue\u2010induced nicotine\u2010seeking behavior.\n                  <\/jats:p>","DOI":"10.1111\/adb.12797","type":"journal-article","created":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T19:58:27Z","timestamp":1563825507000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Accumbens neuroimmune signaling and dysregulation of astrocytic glutamate transport underlie conditioned nicotine\u2010seeking behavior"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6058-7120","authenticated-orcid":false,"given":"Mark D.","family":"Namba","sequence":"first","affiliation":[{"name":"Department of Psychology Arizona State University  Tempe AZ 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