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Opioid withdrawal induces oxidative stress and disrupts glutamate and glutathione homeostasis. We hypothesized that <jats:italic>N<\/jats:italic>-acetylcysteine (NAC) administered during acute opioid withdrawal in neonatal rats would decrease withdrawal behaviors and normalize CNS glutathione and glutamate.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Osmotic minipumps with methadone (opioid dependent, OD) and saline (Sham) were implanted into Sprague Dawley dams 7 days prior to delivery. Pups were randomized to receive either naloxone plus saline or NAC (50\u2013100\u2009mg\/kg), administered on postnatal day (PND) 7. We performed MR spectroscopy on PND6\u20137 before, 30\u2009min, and 120\u2009min after withdrawal. On PND7, we assessed withdrawal behaviors for 90\u2009min after naloxone administration and summed scores during peak withdrawal period.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Mean summed behavioral scores were significantly different between groups (<jats:italic>\u03c7<\/jats:italic><jats:sup>2<\/jats:sup> (2)\u2009=\u200910.49, <jats:italic>p<\/jats:italic>\u2009=\u20090.005) but not different between NAC\/NAL\/OD and Sham (<jats:italic>p<\/jats:italic>\u2009=\u20090.14): SAL\/NAL\/OD\u2009=\u200917.2\u2009\u00b1\u20094.2 (<jats:italic>n<\/jats:italic>\u2009=\u200910); NAC\/NAL\/OD\u2009=\u200911.3\u2009\u00b1\u20095.6 (<jats:italic>n<\/jats:italic>\u2009=\u20099); Sham\u2009=\u20096.5\u2009\u00b1\u20090.6 (<jats:italic>n<\/jats:italic>\u2009=\u20094). SAL\/NAL\/OD pups had decreased glutathione at 120\u2009min (<jats:italic>p<\/jats:italic>\u2009=\u20090.01), while NAC\/NAL\/OD pups maintained pre-withdrawal glutathione (<jats:italic>p<\/jats:italic>\u2009=\u20090.26).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In antenatal OD, NAC maintains CNS glutathione and mitigates acute opioid withdrawal in neonatal rats. This is the first study to demonstrate acute opioid withdrawal neurochemical changes in vivo in neonatal OD. NAC is a potential novel treatment for NAS.<\/jats:p>\n<\/jats:sec>","DOI":"10.1038\/s41390-019-0728-6","type":"journal-article","created":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T12:02:35Z","timestamp":1579003355000},"page":"77-84","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["N-acetylcysteine mitigates acute opioid withdrawal behaviors and CNS oxidative stress in neonatal rats"],"prefix":"10.1038","volume":"88","author":[{"given":"Price","family":"Ward","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hunter G.","family":"Moss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Truman R.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Kalivas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothea D.","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,1,14]]},"reference":[{"key":"728_CR1","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1038\/jp.2015.36","volume":"35","author":"SW Patrick","year":"2015","unstructured":"Patrick, S. 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