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Studies show that brain oxidative stress is consistently associated with alcohol\u2010induced neuroinflammation, and literature implies that oxidative stress and neuroinflammation perpetuate each other. In line with a self\u2010perpetuating mechanism, it is hypothesized that inhibition of either oxidative stress or neuroinflammation could reduce chronic alcohol intake and relapse. The present study conducted on alcohol\u2010preferring rats shows that chronic ethanol intake was inhibited by 50% to 55% by the oral administration of low doses of either the antioxidant N\u2010acetylcysteine (40 mg\/kg\/d) or the anti\u2010inflammatory aspirin (ASA; 15 mg\/kg\/d), while the co\u2010administration of both dugs led to a 70% to 75% (<jats:italic>P<\/jats:italic> &lt; .001) inhibition of chronic alcohol intake. Following chronic alcohol intake, a prolonged alcohol deprivation, and subsequent alcohol re\u2010access, relapse drinking resulted in blood alcohol levels of 95 to 100 mg\/dL in 60 minutes, which were reduced by 60% by either N\u2010acetylcysteine or aspirin and by 85% by the co\u2010administration of both drugs (blood alcohol: 10 to 15 mg\/dL; <jats:italic>P<\/jats:italic> &lt; .001). Alcohol intake either on the chronic phase or following deprivation and re\u2010access led to a 50% reduction of cortical glutamate transporter GLT\u20101 levels, while aspirin administration fully returned GLT\u20101 to normal levels. N\u2010acetylcysteine administration did not alter GLT\u20101 levels, while N\u2010acetylcysteine may activate the cystine\/glutamate transport xCT, presynaptically inhibiting relapse. Overall, the study suggests that a neuroinflammation\/oxidative stress self\u2010perpetuation cycle maintains chronic alcohol intake and relapse drinking. The co\u2010administration of anti\u2010inflammatory and antioxidant agents may have translational value in alcohol\u2010use disorders.<\/jats:p>","DOI":"10.1111\/adb.12853","type":"journal-article","created":{"date-parts":[[2019,11,16]],"date-time":"2019-11-16T06:54:49Z","timestamp":1573887289000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Aspirin and N\u2010acetylcysteine co\u2010administration markedly inhibit chronic ethanol intake and block relapse binge drinking: Role of neuroinflammation\u2010oxidative stress self\u2010perpetuation"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3468-7966","authenticated-orcid":false,"given":"Yedy","family":"Israel","sequence":"first","affiliation":[{"name":"Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine University of Chile  Santiago 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