{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:55:50Z","timestamp":1789430150891,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,2,25]],"date-time":"2014-02-25T00:00:00Z","timestamp":1393286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA026254"],"award-info":[{"award-number":["DA026254"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA015369"],"award-info":[{"award-number":["DA015369"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA003906"],"award-info":[{"award-number":["DA003906"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2015,3]]},"abstract":"Abstract<\/jats:title>\n \n Both pre\u2010clinical and clinical studies indicate that\n N<\/jats:styled-content>\n \u2010acetylcysteine (\n NAC<\/jats:styled-content>\n ) may be useful in treating relapse to addictive drug use. Cocaine self\u2010administration in rats reduces both cystine\u2010glutamate exchange and glutamate transport via\n GLT<\/jats:styled-content>\n \u20101 in the nucleus accumbens, and\n NAC<\/jats:styled-content>\n treatment normalizes these two glial processes critical for maintaining glutamate homeostasis. However, it is not known if one or both of these actions by\n NAC<\/jats:styled-content>\n is needed to inhibit relapse to cocaine seeking. To determine whether the restoration of\n GLT<\/jats:styled-content>\n \u20101 and\/or cystine\u2010glutamate exchange is required for\n NAC<\/jats:styled-content>\n to inhibit cue\u2010induced reinstatement of cocaine seeking, we utilized the rat self\u2010administration\/extinction\/reinstatement model of cocaine relapse. Rats were pre\u2010treated in the nucleus accumbens with vivo\u2010morpholino antisense oligomers targeting either\n GLT<\/jats:styled-content>\n \u20101 or\n xCT<\/jats:styled-content>\n (catalytic subunit of the cystine\u2010glutamate exchanger) overlapping with daily\n NAC<\/jats:styled-content>\n administration during extinction (100\u2009mg\/kg, i.p. for the last 5 days). Rats then underwent cue\u2010induced reinstatement of active lever pressing in the absence of\n NAC<\/jats:styled-content>\n , to determine if preventing\n NAC<\/jats:styled-content>\n \u2010induced restoration of one or the other protein was sufficient to block the capacity of chronic\n NAC<\/jats:styled-content>\n to inhibit reinstatement. The vivo\u2010morpholino suppression of\n xCT<\/jats:styled-content>\n reduced cystine\u2010glutamate exchange but did not affect\n NAC<\/jats:styled-content>\n \u2010induced reduction of reinstated cocaine seeking. In contrast, suppressing\n NAC<\/jats:styled-content>\n \u2010induced restoration of\n GLT<\/jats:styled-content>\n \u20101 not only prevented\n NAC<\/jats:styled-content>\n from inhibiting reinstatement, but augmented the capacity of cues to reinstate cocaine seeking. We hypothesized that the increased reinstatement after inhibiting\n NAC<\/jats:styled-content>\n induction of\n GLT<\/jats:styled-content>\n \u20101 resulted from increased extracellular glutamate, and show that augmented reinstatement is prevented by blocking\n mGluR5<\/jats:styled-content>\n . Restoring\n GLT<\/jats:styled-content>\n \u20101, not cystine\u2010glutamate exchange, is a key mechanism whereby daily\n NAC<\/jats:styled-content>\n reduces cue\u2010induced cocaine reinstatement.\n <\/jats:p>","DOI":"10.1111\/adb.12127","type":"journal-article","created":{"date-parts":[[2014,2,25]],"date-time":"2014-02-25T22:27:56Z","timestamp":1393367276000},"page":"316-323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":173,"title":["Glutamate transporter\n GLT<\/scp>\n \u20101 mediates\n N<\/scp>\n \u2010acetylcysteine inhibition of cocaine reinstatement"],"prefix":"10.1111","volume":"20","author":[{"given":"Kathryn J.","family":"Reissner","sequence":"first","affiliation":[{"name":"Department of Neurosciences Medical University of South Carolina Charleston SC USA"},{"name":"Department of Psychology University of North Carolina Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra D.","family":"Gipson","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Medical University of South Carolina Charleston SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuong K.","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Medical University of South Carolina Charleston SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori A.","family":"Knackstedt","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Florida Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Scofield","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Medical University of South Carolina Charleston SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter W.","family":"Kalivas","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Medical University of South Carolina Charleston SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-007-0753-8"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1069"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(99)80043-9"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2013.01.001"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.003889"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(00)00067-8"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.100057"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.02.049"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(91)90296-A"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220591110"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2012.12010055"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2515"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2011.46"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.06.010"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.07.018"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2009.03.039"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2011.10.024"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1521-0391.2013.12034.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4391"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2006.10.001"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.151357"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.081521"},{"key":"e_1_2_6_24_1","first-page":"265","article-title":"N\u2010acetylcysteine: multiple clinical applications","volume":"80","author":"Millea PJ","year":"2009","journal-title":"Am Fam Physician"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1007-05.2005"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2250"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1011265108"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2011.04.015"},{"key":"e_1_2_6_29_1","volume-title":"The Rat Brain in Stereotaxic Coordinates","author":"Paxinos G","year":"2005"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-012-2837-3"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3452-10.2011"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2011.10.009"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2013.223"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.10.007"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1746-09.2009"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agr023"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.66"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1976-12.2012"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1369-1600.2011.00432.x"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2010.01.013"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2007.06.008"}],"container-title":["Addiction Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fadb.12127","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.12127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T20:32:16Z","timestamp":1696365136000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/adb.12127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2,25]]},"references-count":40,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1111\/adb.12127"],"URL":"https:\/\/doi.org\/10.1111\/adb.12127","archive":["Portico"],"relation":{},"ISSN":["1355-6215","1369-1600"],"issn-type":[{"value":"1355-6215","type":"print"},{"value":"1369-1600","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2,25]]},"assertion":[{"value":"2014-02-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}